TW201019951A - Novel semi-synthetic glycopeptides as antibacterial agents - Google Patents

Abstract

Semi-synthetic glycopeptides having antibacterial activity are described, in particular, the semi-synthetic glycopeptides described herein are made by chemical modification of the a glycopeptide (Compound A, Compound B, Compound H or Compound C) or the monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in acidic medium to give the amino acid-4 monosaccharide; conversion of the monosaccharide to the amino-sugar derivative; acylation of the amino substituent on the amino acid-4 amino-substituted sugar moiety on these scaffolds with certain acyl groups; conversion of the amide group in amino acid-3 on these scaffolds to various acylamide, acylsulfonamide, acylsulfonylurea derivatives; aminomethylation with substituent containing sulfonamide or acylsulfonamide group on amino acid -7 through Mannich reaction; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.

Description

201019951 VI. Description of the invention: [Technical field to which the invention pertains] The invention described herein is a semi-synthetic glycopeptide having antibacterial activity, a pharmaceutical composition comprising the same, and a medical treatment method. This application claims priority to US Provisional Application No. 61/108,446, filed on October 24, 2008, and 61/110,447, filed on October 31, 2008, both of which are incorporated by reference in its entirety. reference. [Prior Art] The emergence of drug resistant strains has reinforced the need for synthesis and confirmation of antibiotics having improved activity. Naturally occurring and semi-synthetic glycopeptide antibiotics for combating bacterial infections include the following compounds, such as vancomycin, deacetylvancomycin, errimycin, and teicosin (complex of five compounds), Dalbavancin, oritavancin, telavancin, and A82846B (LY264826) with structures A, B, C, D, E, F, G and ::

144087-SP-20091119-1 201019951

The microbial agent is infected with (4) and lion fine 11 but with other anti-fine, 'strains with resistance or insufficient sensitivity to these compounds have been confirmed'. These compounds have been found to have resistance to certain bacteria, limited For example, it is resistant to S. aureus infection caused by Staphylococcus aureus which is resistant to compound resistance, or infection by Enterococcus which is resistant to Compound A. 144087-sp-20091119-1 201019951 SUMMARY OF INVENTION [In particular, bacterial infections] and methods of using the compounds to treat and/or prevent diseases. In one aspect, the compounds described herein are compounds formed by the modification of the backbone of Compound A, Compound B, Compound C or Compound 11 to provide novel semi-synthetic glycopeptides having anti-fine g activity, and pharmaceutics thereof. Acceptable salts, vinegars, solvates, quaternized ammonium salts, stereoisomers, tautomers or prodrugs thereof, and which in some embodiments are antibacterial agents, It is used to treat bacterial infections and has superior microbiological and pharmacokinetic properties' to outperform the glycopeptide antibacterial agents currently available. In one aspect, the compounds described herein are compounds having a structure selected from the group consisting of: (I-V):

144087-SP-20091119-1 201019951

HO .Re

Wherein ra is selected from the group consisting of a) hydrogen, b) methyl, c) C2_Ci 2_alkyl; l and R2 are each independently selected from the group consisting of a) hydrogen, b) CVCu-alkane a group, c) a q-Cu-alkyl group substituted by one or more substituents selected from the group consisting of (8) halogen, (b) hydroxyl group, 144087-SP-20091119-1 -7-201019951 (c Ci-C12-alkoxy, (6) CVC: 3-alkoxy_Cl_C3-alkoxy, (6) amine, 1q-Cu•alkylamino, (g) q-Cu-dialkylamino, (h) Alkenyl, (i) alkynyl, 1Q-Cu-thioalkoxy, d) q-Cu•alkyl substituted by aryl, e) Ci_Ci2_alkyl substituted by substituted aryl, f) Substituted by a heteroaryl group (^-(:12-alkyl, g) substituted by a substituted heteroaryl group of Ci_Ci2_alkyl, h) cycloalkyl, i) cycloalkenyl, J) heterocycloalkyl , or

Ri is employed together with R2 and the atoms to which they are attached to form a substituted heteroaryl or M0 membered heterocycloalkyl ring, optionally containing one or two heterofunctional groups selected from the group consisting of: - 0-, -NH, -NA-CV alkyl)-, -N(aryl)-, _N(aryl-C6-alkyl-)-, _n(substituted-aryl-q-C6-alkyl _)_, -N(hetero)-, _n(heteroaryl-Q-C6_alkyl)_,_n(substituted-hetero-based-C^-C6-alkyl-)-,- S- and S(0)n - wherein n is 1 or 2' and the 3-10 membered heterocycloalkyl ring system is optionally substituted by one or 144087-SP-20091119-1 -8 - 201019951 multiple substituents The substituents are independently selected from the group consisting of (a) _, (b) hydroxy, (6) C! -C3 - alkoxy, (d) Q-C3-alkoxy_Cl_c3-alkoxy, (e ) _ base,

1 calcining group, (8) q-c3 haloalkyl, (h) Ci-Cr alkoxy _Ci_c3_alkyl, and k) C(=〇)r7, 1}, wherein r8, uldent 9 and ulnar Independently selected from the group consisting of argon, lower alkyl, substituted

Lower alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, or ~ and ~. Used together with the atoms to which they are attached, forming a 3-10 membered heterocycloalkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of (8) _, (b) ) hydroxy, (c) G-C3 - alkoxy, (6) CA methoxy _Ci_C3_ alkoxy, 144087-SP-20091119-1 -9- 201019951 (e) keto, (f) cvcv alkyl, ( g) Cl -C3 haloalkyl ' (h) CVCV alkoxy-Ci-CV alkyl; R7 is selected from the group consisting of a) hydrogen, b) Ci -Ci 2 -alkyl 'c) Or a plurality of substituent-substituted q-Cu-alkyl groups, the substituents being selected from the group consisting of (8) halogens, (8) mercapto groups, (c) CVCu-alkoxy groups, (6) cvcv alkoxy-eve-alkoxy groups , (6) Amino, (f) Cl-Cl 2 -Acetylamine, (g) Ci_C丨2_di-s-amine '(8)alkenyl, (i) alkynyl, 1Cl -Cl 2 _thioxolynoxy' d) q-Cu-alkyl substituted by aryl, e) substituted aryl substituted alkyl, f) substituted by heteroaryl - 匸丨 烷基, g) substituted hetero Substituted q 2-alkyl, h) cycloalkyl, 144087-SP-20091119-1 -10- 201019951 i) cycloalkenyl, j) heterocycloalkyl, k) Ci-Ci 2 -Acetylamine, l) Amine, m) Amino-cycloalkyl; X is selected from the group consisting of (1) hydrogen, (2) chlorine; Y is selected from the group consisting of (1) oxygen, (2) NRi, whose center is as defined above; T is selected from the group consisting of (1)-so2rb, (2) -CORB, (3) -C0NHS02Rb; R is selected from the group consisting of (1) hydrogen, (2) ring Alkyl, (3) cycloalkenyl, (4) CVCu-alkyl, (5) q-Cu-alkyl substituted by one or more substituents selected from the group consisting of (8) halogen, ( b) Mercury, 144087-SP-20091119-1 -11 - 201019951 (6) CVCu-alkoxy, (d) Ci-C3 - alkoxy _Ci-C3 - alkoxy, (e) -COOR5 'where & Is hydrogen or low carbon, (f) -C(0)NR5 R·6 'where Rs is as defined above, and the heart is hydrogen or low carbon alkyl* (g) amine group, (h) -NR5 Rg 'wherein Rs and R_6 are as defined above, or & and Re and the atom to which they are attached, form a 3-10 membered heterocycloalkyl ring, which is optionally substituted with one or more substituents, The substituents are independently selected from the group consisting of (i) halogen, (8) hydroxyl, (iii) Ci-C3 - Oxyl, (iv) Q-Cr alkoxy-q-Cr alkoxy, (v) keto, (vi) q-Cu-alkyl, (vii) Cl_Cl2i alkyl, and (Mi) CVCV _Cl_Ci2_alkyl, (i) aryl, 1 substituted aryl, (k) heteroaryl, (l) substituted heteroaryl, 144087-sp-20091119-l -12· 201019951 @1 Amidino, (n) CVCu-thioalkoxy, (6)C(=〇)ORi 1 ' wherein Ri 1 is hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted aryl , heteroaryl or substituted heteroaryl, (7) C(=〇)NRnR12 ' wherein Ru is as defined above, and Re is hydrogen, lower alkyl, substituted lower alkyl, aryl,

Substituted aryl, heteroaryl or substituted heteroaryl, or

Ru is employed together with Ru and the atoms to which they are attached to form a 3 10 membered heterocycloalkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of the following constituents (8). (9) Hydroxy, (C) C! -C3 - alkoxy,

(d) ^-^-alkoxy^^^-alkoxy, (e) keto, 1 C! -C! 2 -alkyl, (g) substituted lower alkyl, (9)^-( :^haloalkyl, (i) amine group,

Ci) Acrylamine, (k) Dialkylamino and 144087-sp-20091119-1 • 13- 201019951 1(:1-€3-Alkoxy<:1-(:12-alkyl, or R The oxygen atom to which it is attached is used together as a halogen; R3 is selected from the group consisting of (1) OH, (2) 1-adamantanamine, (3) 2-adamantanyl, (4) 3-amino- 1-adamantanylamino, (5) 1-amino-3-adamantanylamino, (6)3-lower leucine-l-adamantylamine, (7)1-lower alkylamino-3-adamantamine (8) Amino (9) NR! 3 core 4 ' wherein & 3 and h * are each independently selected from the group consisting of hydrogen, low carbon alkyl, substituted low carbon alkyl, cycloalkyl, substituted a cycloalkyl group, an amine lower alkyl group, wherein the amine moiety of the amine lower alkyl group is further substituted or unsubstituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl An aryl group, an alkoxy aryloxy group, a substituted alkoxy group, and a substituted aryloxy group or

Ri3 is used together with Ri4 and the atoms to which they are attached to form a 3_1 member heterocyclic alkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of the following groups: (9) Meridian, 144087-SP-20091119-1 201019951 (c) Ci-CV alkoxy, (d) q-cv alkoxy-qq-alkoxy, (e) keto, (f) CVCu-alkane Base, (g) substituted lower alkyl, (h) q-Cui alkyl, (1) amine, Φ

1 alkylamino, (k) dialkylamino and (l) CVCV alkoxy-CVCu-alkyl; R4 is selected from the group consisting of (1) CH2NH-CHR15-(CH2)m-NHS02RB, which makes melon Is j to 6, and R15 is deuterium or lower alkyl, (2) CH2 NH-CHR! 5 -(CH2)p -C0NHS02 RB, wherein ρ is 〇 to 6, and R15 is hydrazine or lower alkyl, (3) CH2NH-CHR15-(CH2)pC〇〇H, where ρ is 〇 to 6, and Ri 5 is Η or lower carbon, (4) CH2 NRD -CHR! 5 -(CH2 )q -NRE S02 RB, Wherein q is 2 to 4, and Ri 5 is H or a low carbon alkyl group, RD and RE together represent -, (5) Η, (6) CH2NHCH2P03H2, (7) an amine lower alkyl group, wherein the amine lower alkane The amino group of the group is further substituted or unsubstituted alkyl, dilute, cyclized 144087-SP-20091119-1 -15-201019951, cycloalkenyl, arylaryl, alkoxy, An aryloxy group, a substituted alkoxy group, and a substituted aryloxy group; rb is selected from the group consisting of a) an aryl group, b) a Ci-C! 2 -alkyl group, C) is one or more Substituent substituted q-C! 2-alkyl, the substituent is selected from the group consisting of (8) halogen, (b) hydroxyl, (c) q -c12-alkoxy, (d) QC: 3-alkoxyoxy, (8) amine, (f) C--C12-anilino, (g)-dialkylamino, (9) dilute, 1 Alkynyl, 1(ν〇:12-thioalkoxy, d) Cl_Cl2•alkyl substituted by aryl, e) q-C! 2-alkyl substituted by substituted aryl, 0 is hetero Aryl substituted alkyl, g) Ci_C12 alkyl substituted by substituted heteroaryl, h) cycloalkyl, i) heteroaryl, J) heterocycloalkyl, 144087-sp-20091119-1 -16- 201019951 k) an aryl group substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxyl, (6) q-Cu-alkoxy, (6) q-Q-alkoxy -q-CV, alkoxy, (6)amino, 1amino-CVCV alkoxy, (g) (^-(:12-anilino, (h) Ci-Cn-alcoholyl-.-(^ - alkoxy, 1Cl-Ci 2-diamine, 1C1-C12-dialkylamino-CpCV alkoxy, (9) alkenyl, (l) alkynyl, (m) Cl -Ci 2 - thiopyr Oxy, ❹ (8) CVCu-alkyl, (〇) C1-C12-substituted alkyl, (P) C1 -C1 2 -homolyl-moffinyl, (q) Cl-Cl2_alkoxy_C1_C12 -dialkoxyamino, (r) C1-C12-alkoxy-NHSOA-CV An alkyl group, (8) cvc12-alkoxy-nhcocvcv alkyl; 1} a heteroaryl group substituted by one or more substituents selected from the group consisting of (a) _, 144087-SP-20091119-1 •17· 201019951 (9) hydroxy, (c) q-Cu-alkoxy, (d) CVQ-alkoxy-CVQ-alkoxy, (6) amine, (f) amino-q-cv alkoxy, (g) C丨-C12-Acrylamine, (8) q-Cu-alkylamino-cvQ-alkoxy, (i) (ν<:12-dialkylamino, 1q-Cu-dialkylamino-CVCV Alkoxy, (k) alkenyl, (l) alkynyl, (in) Ci -Ci 2 - thioxyloxy, (8) Ci-Ci 2-alkyl group (o) CVCu-substituted alkyl;

The Re is each independently selected from the group consisting of a) hydrogen, b) Ci-Ci 2 -alkyl 'c) a q-Cu-alkyl substituted by one or more substituents selected from the group consisting of Group (8) Halogen, (b) Hydroxy, (C) Ci-C! 2_Alkoxy, (6) Ci-cv alkoxy-CVC3-alkoxy, (6) Amine* 144087-SP-20091119-1 -18- 201019951 (7) Ci-C12-alkylamino, (g) C1 -C1 2 -dialkylamine, (9)alkenyl, 1 alkynyl, 1Cl 2 -thio alkoxy, d) Cl_Cl 2 -alkyl substituted by aryl , 6) Substituted by a substituted aryl group (^-(:12-alkyl, @f) is substituted by a heteroaryl group (^-(:12-alkyl, g) is substituted by a substituted heteroaryl group Ci_Ci2_alkyl, h) cycloalkyl, i) cycloalkenyl, heterocycloalkyl, k) C(=0)R7, wherein r7 is previously defined, 1} C(=〇KHR8NR9R10, where r8 And R9&Ri(R) are each independently selected from the group consisting of hydrogen, lower alkyl, substituted fluorene lower alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl The base, or the atom and the atom to which they are attached, are used to form a 3-10 membered heterocyclic ring, depending on the situation. Substituted by _ or a plurality of substituents, the substituents are independently selected from the group consisting of (8) halogen, (b) hydroxy, (c) C]-C3 - alkoxy, I44087-SP-2009I119-I -19- 201019951 (6) cvcv alkoxy-eves-alkoxy, (6) keto, 7q-cv alkyl, (g) c--c3 haloalkyl, (8) q-cv alkoxy-q-cv alkyl; or pharmaceutically thereof Acceptable salts, esters, solvates, alkylated quaternary ammonium salts, stereoisomers, tautomers or prodrugs. In further embodiments, the compounds have the structure of Formula I

R

Or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein R or the like has the meaning as defined herein. In a further embodiment, the compound has the structure of formula II

Or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein K 144087-sp-20091119-l -20- 201019951 Etc. has the meaning as defined herein. In a further embodiment, the compound has the structure of formula III

Or a pharmaceutically acceptable salt, vinegar, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein ra or the like has the meaning as defined herein. In a further embodiment, the compound has the structure of Formula IV

Or a pharmaceutically acceptable salt, vinegar, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein Rc or the like has the meaning as defined herein. In a further embodiment, the compound has the structure of formula V 144087-sp-20091119-1 -21- 201019951

Or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein Han et al. have the meaning as defined herein. A In a further embodiment of any of the above structures, which is methyl, R4 is hydrogen. In another embodiment, 'ra is hydrogen and & is gas. In another specific embodiment, X is hydrogen and I is hydrogen. In another embodiment, X is gas ' and R4 is hydrogen. In another embodiment, ra is methyl' and R4 is CH2NHCH2P〇3H2. In another embodiment, RA is hydrogen and R4 is CH2NHCH2P〇3H2. In another specific example, RA is hydrogen and R4 is CH2NH-CHR15-(CH2)m-NHS02RB, where m is from 1 to 6, and R!5 is a ruthenium or a low carbon yard. In another embodiment, ra is a fluorenyl group and R4 is CH2NH-CHR15-(CH2)m-NHS02RB, wherein, for example, 1 to 6' and R!5 is hydrazine or lower alkyl. In another specific embodiment, Ώ is hydrogen and R4 is ch2nh-chr15-(ch2)p-conhso2rb, wherein p is 〇 to 6, and R15 is fluorene or lower alkyl. In another specific embodiment, Ra is methyl and R4 is CH2NH-CHR15-(CH2)p-COSOCS02RB, wherein p is from 〇 to 6, and R15 is deuterium or lower alkyl. In another specific embodiment, ra is hydrogen and R4 is CH2NRD-CHR15-(CH2)q-NRES02RB ' wherein q is 2 to 4 and R15 is deuterium or lower alkyl, and RD is represented together with Re CH2-. In another embodiment of 144087-sp-20091119-1 -22-201019951, ra is methyl, and R^CHzNRD-CHRB-CCHdq-NRE S〇2 Rb ' wherein q is 2 to 4, and 1^ 5 is η or low charcoal base ' Rd together with Re to represent -CH2-. In a further embodiment of any of the foregoing specific embodiments, R3 is selected from the group consisting of (1) OH, (2) 1-adamantanyl, (3) 2-adamantanyl, (4) 3-amine Alkyl-adamantanylamino, (5) 1-amino-3-adamantanylamino, (6)3-lower alkylamino-1-adamantanylamino, (7) 1-lower alkylamino- 3-adamantylamino, (8) Amino (9) NUh, wherein r13 and r14 are each independently selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, naphthoquinone a substituted, cycloalkyl group, an amine-based lower alkyl group, wherein the amine moiety of the amine lower alkyl group is further unsubstituted or substituted with an alkyl, alkenyl, cycloalkyl, or ring of r Alkenyl, arylaryl, alkoxy, aryloxy, substituted alkoxy and substituted aryloxy or substituted! ^4 together with the atoms to which they are attached form a 31-membered heterocycloalkyl ring which is optionally substituted by one or more substituents independently selected from the group consisting of the following constituents (8)-, 144087-SP -20091119-1 -23- 201019951 (b) hydroxy, (4) Ci-C3 morphine, (d) Ci-q-alkoxy _Cl_C3 methoxy, (4) yl, 1C1_C12-alkyl, (g) Substituted lower alkyl, (8)-C1 2 haloalkyl, 1 amino group, 1 alkylamino group, (k)-amine group and W ii-C3-alkoxy_Cl_Cl2_alkyl group. In the specific embodiment, in the other embodiment, in the other item, 3 is 2_Jingan 1 (10) amine group. In another specific embodiment, only 3 is an amine group H step to implement the financial Diethylamine. In the other specific examples, 'R3 is dimethylaminoethylamine. In another specific embodiment, N.methylhexa-- is applied to any of the specific references mentioned in the text. In a further embodiment of the present invention, & and ruler 2 are each independently selected from the group consisting of lower ribs a) hydrogen, b) q2 -alkyl, c) Cl_Cl2_alkan substituted by one or more substituents a substituent selected from the group consisting of (a) _, 144087-SP-20091119-1 -24- 201019951 (9) hydroxy, (c) CVC^-alkoxy, (d) Q-C3 - oxygenated -q-C3 - alkoxy, (e) amine, (f) Cl-Cl 2 - acryl, (g) Cl-Cl 2-diamine, (h) alkenyl, (1) fast radical ,

(j) CVCu-thioalkoxy, d) Ci-Cu-alkyl substituted by aryl, e) substituted by substituted aryl (^-(:12-alkyl, f) Substituted by 0^-(:12-alkyl, g) Cl_c12-alkyl substituted by substituted heteroaryl, h) cycloalkyl, i) cycloalkenyl,

J) a heterocycloalkane, or a heart and a stalk of 2 and the atoms to which they are attached, forming a substituted heteroaryl or a 3-1 membered heterocycloalkyl ring, optionally containing one or two a heterofunctional group selected from the group consisting of: _<>, _NH, _N(ci-C6-alkyl)-, -N(aryl)-, -N(aryl-Cl _C6_Hyun* -) _, -N (substituted-aryl-Q-C6-alkyl'-N(heteroaryl), _N(heteroaryl-C6-homo-)-, -N (substituted-heteroaryl) a group of _Ci-C6-alkyl and -S-ORS(〇)n-, wherein η is 1 144087-sp-20091119-l -25, 201019951 or 2' and the 3-10 membered heterocycloalkyl ring system The situation is replaced by one or more substituents. The substituents are independently selected from the group consisting of (a) 13b, (b) hydroxyl, (c) C1-C3-alkoxy, (9) Ci-C3-alkoxy (6), (7) q-cv alkyl, (g) ci-C3 haloalkyl, (h) ci-c3-alkoxy-q-cv alkyl, and k) C(=0)R7, l ChCOCHRsNRgl^o ' wherein r8, r9 and R1 are each independently selected from the group consisting of hydrogen, low carbon alkyl, substituted low carbon alkyl, aryl, substituted aryl, heteroaryl Or substituted heteroaryl, A is used together with R10 and the atoms to which they are attached to form a 3-10 membered heterocyclic alkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of the following: (8) , (b) hydroxy, (c) C! -C3 - alkoxy, (d) Q-C3 - alkoxy-C3 - alkoxy, (6) keto, 144087-sp-20091119-1 -26- 201019951 1cvcv alkyl, (g) cvq haloalkyl, (h) q-cv alkoxy-CVC3-alkyl. In a further embodiment of the specific embodiments mentioned above, ", 4 hydrogen. In another specific embodiment towel, R1AC1_C "院院,

In another embodiment, & is substituted by an aryl or substituted alkyl group, and R2 is hydrogen. In another embodiment, I is c(=0)Cl_Cl2_alkyl and is converted to hydrogen. In another specific embodiment, h is C^OXTI^NHCi2-alkyl and R2 is hydrogen. In another embodiment, the R'Cl_Cl2 filaments are burned, and the % is hydrogen. In another specific embodiment, the core is a Ci-Ci2 thioalkoxy substituted q-Q2-alkyl group, and & is hydrogen. In another specific embodiment, the ruler 1 is a 〇1 <:12-alkylamino substituted Cl_Cl2_alkyl group, and & is hydrogen. In a further embodiment of any of the specific embodiments mentioned in the text, R is selected from the group consisting of

(1) hydrogen, (2) cycloalkyl, (3) cycloalkenyl, (4) Cl -Cl 2 -alkyl, (3) C1_C12-alkyl substituted by one or more substituents, the substituent being selected from the group consisting of the following (8) Halogen, (b) Hydroxy, (c) Q-Cu-alkoxy, 144087-sp-20091119-l • 27- 201019951 (d) C! -C3 - alkoxy-C! -C3 - alkoxy , (6)-COOR5 'wherein R5 is hydrogen or lower alkyl, (f) -C(0)NR5 Rg ' is as defined above and is hydrogen or lower alkyl, (g) amine group, (h) -NRSR6, wherein Rs is employed together with a core as defined above, or with an atom of 5 and 6 and 4 attached to form a 3-10 membered heterocycloalkyl ring, optionally substituted by one or more substituents. Substituted, the substituents are independently selected from the group consisting of (i) halogen, (8) hydroxyl, W q-CV alkoxy, (iv) qQ-alkoxy_Ci_C3_alkoxy, (v) keto, ( Vi) Ci-Ci 2 -alkyl, (VU) C! -Ci 2 _ alkyl, and (viii) q-CV alkoxy „Cl_Ci2_alkyl, (1) aryl, 1 substituted aryl, ( k) heteroaryl, (l) substituted heteroaryl, (m) fluorenyl, 144087-sp-20091119-l -28- 201019951 (8) G 2 -thio alkoxy, (6) C(=〇)〇Ru, wherein ru is hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, (7)c (=o Nrur12, wherein Ru is as defined above and is hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted, heteroaryl or substituted heteroaryl, or Together with the atoms to which the heart 2 and the other are attached, form a 3_1 member heterocycloalkyl ring, which is optionally substituted with one or more substituents independently selected from the group consisting of the following components: (8) pixels, (b ) hydroxy, (c) G - C3 - alkoxy, (d) Ci - C3 - alkoxy-Ci - C3 - alkoxy, (e) fluorenyl, (f) Ci -Ci 2 , (g) substituted lower alkyl, (h) Ci-C! 2 haloalkyl, (i) amine, 1 alkylamino, (k) dialkylamino and (1) (^-(^- Alkoxy-^-匚^-alkyl, 144087-SP-20091119-1 -29- 201019951 or R and its attached oxygen atom together are employed as a halogen. Further, further embodiments of the specific embodiments mentioned hereinabove In the example, R is 虱. In another specific embodiment, the ruler is wide. Based on the other - Item particular embodiment, R is a substituted aryl group or substituted aryl group of the group. In another specific embodiment, the base is burned. In another embodiment, R is (10))NHCl-Cl 2 substituted with an aryl or substituted aryl group. In another embodiment (IV), r 4 C(=〇)〇Cl _Cl 2 —alkyl group. In another specific embodiment, R is c(=〇)NHCi_Cipolyalkyl substituted with a heteroaryl or substituted heteroaryl. In any of the specific embodiments of any of the foregoing specific examples, the B is selected from the group consisting of a) aryl, b) Cl-C12-alkyl, hydrazine- or more than one trans-radical Substituted, the substituent is selected from the group consisting of (4) alizarin, (b) hydroxyl, (e) Ci-C! 2 - daheptyloxy, (d) Cl'C3_alkoxy-< VC3-alkoxy, (e) amine, 7Cl-C! 2-alcoholyl, (g) Cl-C12-dialkylamino, (8) alkenyl, 144087-sp-20091119-l 201019951 (i) alkyne Base, G) < ν (: 12-thioalkoxy, d) q-Cu-alkyl substituted by aryl, e) substituted aryl substituted alkyl, f) substituted by heteroaryl Heart-heart alkyl, g) q-Cu-alkyl substituted by substituted heteroaryl, h) cycloalkyl, i) heteroaryl,

j) heterocycloalkyl, k) an aryl group substituted by one or more substituents selected from the group consisting of (8) ii, (b) hydroxy, (c) Ci-Cia-alkoxy' (6) Ci -Cg - alkoxy-Ci-Cg - alkoxy"

(6) Amine group, (f) Amino-Cl-C6-alkoxy (g) Ci-Cu-alkylamino group, (h) q-Cu-alkylamino-Ci-cv alkoxy group, (i) q -Cu-dialkylamino, 1Ci-Cu-dialkylamino-Ci-Q-alkoxy, (k) alkenyl, (l) alkynyl, (m) Ci-Ci 2 thio- alkoxy , 144087-sp-20091119-l -31-201019951 (8)Q-Cu-alkyl, (6)C!-Ci 2 -substituted alkyl, (P) Ci-Ci 2_alkoxy-?? 11 base, (q q -c〗 2 -Alkoxy-c! 2 -di-s-oxyalkylamino, (r) Ci-Cu-alkoxy-NHSC^q-Cp-alkyl, (8)q-Cu-alkoxy-NHC0Cl_C6 a heteroaryl group substituted with one or more substituents selected from the group consisting of (8)-, (b) hydroxy, (c) Ci 2 -alkoxy, (d) Q-cv alkoxy _Cl_C6_^oxy, (e) amine group, (f) amino-q-cv alkoxy group, (g) CpCu-alkylamino group, (8) q-Cu-alkylamino group _Ci_c6_ Alkoxy, (1) (Vc12-dialkylamino, 1Cl_Cl2. dialkylamino-q-cv alkoxy, (k) alkenyl, (l) alkynyl, (10) C1-C12-thioalkoxy, (8)Cl -Cl 2-alkyl, (9) C1_C12-substituted alkyl; further examples of any of the examples mentioned above, A _ ^ In an embodiment, 144087-SP-20091119-1 -32- 201019951 RB is Q-C! 2 -alkyl. In another embodiment, RB is C1_c12 substituted with an aryl group or a square group. In the other embodiment, the heteroaryl group or the substituted (iv) silk group is substituted. In another specific embodiment, 'rb is substituted with an aryl group (^12. In another embodiment, RB is an aryl group substituted by dentate. In the other item =A, rb is a Ci_Ci2-substituted aryl group substituted. In a specific embodiment, Rb is a Cim substituted by an alkoxy group. In the fifth embodiment, RB is a carbonyl group substituted by dentate. In another embodiment, RB is a C1_C12• alkoxy group. Substituted aryl. & A f in the eight-body embodiment, 'RB is Cl_C6' alkoxy_Cl-C6_ alkoxy group, the other side of the specific example, RB is an amine group Cl-C6_^milyl-substituted aryl. In another embodiment, RB is an aryl group substituted with a CrCu-anilino A-cv alkoxy group. In another embodiment, Rb For heteroaryl substituted by heteroaryl hydrazine The Μ㈣ base. In another embodiment, ' Rb is a Cl-Cl2_alkyl group substituted with a heteroaryl group. In the item, in the physical example, 'Rb is a heteroaryl group substituted by dentate. In another specific embodiment, Rb is substituted with a heteroaryl group. In another embodiment, Rb is a heterocyclyl substituted with a substituted Cim. In another embodiment, Rb is a heteroaryl group substituted with a hydroxy group. In another embodiment, Rb is a heteroaryl group substituted by a Ci C6 alkoxy group. In a specific embodiment, the core is an amine group (VCdoxy-heteroaryl). In a specific embodiment, Rj is substituted by a Cl_c12_Acrylamino-Ci_Q_^oxy group. In a further embodiment of the specific embodiment referred to in any of the months, 144087-sp-20091119-1 33- 201019951

Rc is each selected from the group consisting of a) hydrogen, b) Q-C! 2 -alkyl, c) Ci_Ci2 alkyl substituted by one or more substituents selected from the group consisting of the following: (8) _, (b) thiol, (6) Ci-Ci 2 - alkoxy, (d) C1 -c3 - alkoxy-C! -c3 - alkoxy, (6) amine, 1Cl-Cl 2-alcohol , (g) Ci-Cu-dialkylamino, (9) dilute, (1) alkynyl, 1q-Cu-thioalkoxy, d) q-Cu-alkyl substituted by aryl, e) substituted An aryl substituted alkyl group, f) a CVCu-alkyl group substituted by a heteroaryl group, g) a Ci_Ci2_alkyl group substituted by a substituted heteroaryl group, h) a cycloalkyl group, i) a cycloalkenyl group, j) Heterocycloalkyl, k) C(=〇)R7, wherein A is previously defined, l) c(=o)chr8nr9r10, wherein r8, uldent 9 and Ri〇 are independently selected from 144087-SP-20091119-1 -34- 201019951 】Groups. Hydrogen, lower alkyl, substituted low anaalkylaryl, substituted aryl, heteroaryl or substituted heteroaryl, or ~ and heart. Used together with the atoms to which they are connected, forming a 3-10 member heterocyclic ring, which is replaced by - or multiple

Substituent, the substituents are independently selected from the group consisting of (8) halogen, (b) hydroxyl, (6) q-cv alkoxy, (d) Q-C3 - alkoxy-C3 - alkoxy, (e) keto , (ί) Ci -C3 -alkyl, (g) haloalkyl, (h) Q-CV alkoxy-Q-C3-alkyl.

In a further embodiment, Rc is hydrogen. In another embodiment, 'Rc is C! -C〗 2_alkyl. In another specific embodiment, the core is a Cl_Cl2_alkyl group substituted with an aryl or substituted aryl group. In another specific embodiment, RC is a Cl_Ci2-alkyl substituted with a heteroaryl or substituted heteroaryl. In another embodiment, the core is cKci2_alkyl substituted with a halogen. In another embodiment, 'Rc is ChCOCi-C! 2-alkyl. In another specific embodiment, Rc is a ChCOCi^NHCi-Cy alkyl group. In another specific embodiment, the alkyl substituted q-Cu-alkoxy group. In another embodiment, Rc is C! 2 -alkyl substituted Ci-C! 2 - thioxo) oxy 144087-SP-20091119-1 -35- 201019951. In another embodiment, & is <^-(: 12-alkyl substituted qc^-alkylamino. In a further embodiment of any of the above structures, Y is oxygen and r4 is hydrogen In another specific embodiment, Y is NH and R4 is hydrogen. In another specific embodiment, Y is oxygen and R4 is CH2NHCH2P03H2. In another specific embodiment, Y is NH, And R4 is CH2NHCH2P03H2. In a further embodiment, T is -S02RB and R4 is hydrogen. In another specific embodiment, T is -CORB and R4 is hydrogen. In another specific embodiment, T is -C0NHS02RB, and R4 is hydrogen. In another specific embodiment, T is -S02RB and r4 is ch2nhch2po3h2. In another specific embodiment, T is -CORB and r4 is ch2nhch2po3h2. In a specific embodiment, τ is -conhso2rb and r4 is ch2nhch2po3h2. In a further specific embodiment of any of the foregoing specific embodiments, the heart is hydrogen and R2 is COCHRsNHRi 6, wherein Ri6 is substituted An aralkyl group, and R8 is as defined above. On the other hand, it is selected from the group consisting of compound (23), compound (24), Compound (26), compound (27), compound (28), compound (29), compound (30), compound (31), compound (32), compound (33), compound (34), compound (35) , Compound (36), Compound (37), Compound (38), Compound (39), Compound (40), Compound (41), Compound (42), Compound (43), Compound (44), Compound (45) , Compound (46), Compound (47), Compound (48), Compound (49), Compound (50), Compound (51), Compound (52), Compound (53), Compound (54), Compound (55) Compound (56), Compound (57), Compound (58), Compound (59), Compound (60), Compound (61), Compound (62), 144087-SP-20091119-1 • 36-201019951 Compound (64) ), Compound (64), Compound (65), Compound (66), Compound (67), Compound (68), Compound (69), Compound (98), Compound (99), Compound (100), Compound (101) ), compound (102), compound (103), compound (104), compound (105), compound (106), Compound (107), compound (115), compound (116), compound (117), compound (118), compound (119), compound (120), compound (121), compound (122), compound (123) , Compound (124), Compound (125), Compound (126), Compound (127), Compound (143), Compound (144), Compound (145), Compound (150), Compound (151), Compound (152) , Compound (153), Compound (155), Compound (156), Compound (157), Compound (158), Compound (159), Compound (160), Compound (161), Compound (162), Compound (163) a compound of the compound (164), the compound (165) and the compound (166). In another aspect is a pharmaceutical composition comprising a therapeutically effective amount of any of the compounds previously recited, along with a pharmaceutically acceptable carrier or excipient. In another aspect, a method of treating a mammal in need of such treatment, comprising administering to the mammal an antibacterial effective amount of any of the compounds previously mentioned, along with a pharmaceutically acceptable carrier or agent thereof Shape agent. In another aspect, described herein is the use of a compound described herein in the manufacture of a medicament for the treatment of a disease or condition associated with a bacterium. In another aspect, as described herein, the article of manufacture comprises a packaging material, any compound of Formula I, Formula II, Formula, Formula IV or Formula V, which is effective for treating, preventing or ameliorating a disease caused by bacteria or One or more symptoms of the symptom, within the packaging material, and a label indicating the compound or composition of 144087-SP-20091119-1 -37-201019951, pharmaceutically acceptable salt thereof, (iv) acceptable An oxide, a pharmaceutically acceptable thioglycoside metabolite, a pharmaceutically acceptable prodrug or a pharmaceutically acceptable solvate for use in the treatment, prevention or amelioration of a disease or condition mediated by a bacterium One or more symptoms are provided. In another aspect, a method for producing a compound of the formula ι_ν, which comprises: modifying from the formula i, ii

a compound of the group consisting of hi, iv and v,

Wherein RA is hydrogen or fluorenyl 'X is chloro or hydrogen, R3 is OH or alkoxy, 2-adamantanyl or lower alkylamino, as defined herein, hydrogen or suitably protected CH2NHCH2P03H2 or Boc - an amino lower alkyl group, as defined herein, by a technique selected from the group consisting of: (4) 9-fluorenyl oxycarbonyl (Fmoc) or a third-butoxycarbonyl (Boc) or other suitable nitrogen Protecting group, protecting the amine group. (b) making the third amino acid aspartate a guanamine group, rbS02C1, 144087-sp-20091119-l -38· 201019951

KbCOOH, using a coupling reagent, or a rbS〇2_nc〇 group, is deuterated in the presence of a test such as triethylamine, and (c) the protecting group of the amine group is removed. The b〇c protecting group is removed as a mild acid such as diacetic acid, and the Fmoc group is removed as a test such as diethylamine. (Φ, if Rs is an alkoxy group, the acid base is removed by mild base or acid hydrolysis to obtain an acid-lowering derivative, (6) the azide functional group is reduced to an amine, and the monosaccharide is a primary alcohol or The amine group of the fourth amino acid of the compound is substituted with an amine substituent on the sugar moiety to have the structure RJ (wherein J is a halogen), Rl_j (wherein j is a halogen), r2_j (where J is a halogen) or Alkylation of an alkyl halide of RC-J (wherein J is a halogen) (g) substitution of one of the monosaccharides or an amine group on the amine-substituted sugar moiety of the fourth amino acid of the compound a base, brewed with a broth having the structure c(=o)r7, (h) substituted with a monosaccharide of the monosaccharide or an amine group on the amino substituted sugar moiety of the fourth amino acid of the compound a base, which is brewed with a broth having the structure C(=0)CHR8 NR9, (i) an amine group on the amino group of the fourth amino acid of the compound, and an aldehyde or a ketone Reaction, followed by reductive amination of the imine formed, 1 conversion of the acid moiety on the macrocyclic ring of the compound with a substituted decylamine as defined by rule 3 , 144087-SP-20091119-1 -39- 201019951 (k) For the reaction of the mono- or partial amine of the monosaccharide moiety of the fourth amino acid of the compound with the phosgene of the adjacent meridine, (l) for the compound The 7th amino acid, wherein R4 is argon, and NH2-CHR15-(CH2)m-NHS02RB 'NHRD-CHR! 5-(CH2 )q -NRE S02 RB or NH2 -CHR! 5 -(CH2 )p - C0NHS02 RB, Mannich reaction in acetonitrile with water or other suitable organic solvent in the presence of aqueous formaldehyde solution, (m) combination of (8), (b) and (c), combination of (8) (8), (b), (6) and (6), (6) a combination of (8), (b), (6), 1 and (6), (p) a combination of (8), (b), (f) and (8), (q) a combination of (8), (b), (g) and (c), (r) a combination of (8), (8), (8) and (c), (8) a combination of (8), (8), (i) and (c), (t) a combination of (a), (b), (e) and (c), (8) Combination of (8), (9), (6), (6) and (c), (v) (8), (b) '(6), 1, (6) and (6), (w) (a), (8), (6), (e) and (c) a combination of (8) (8), (8), (6), 1, (6), (f) and (6), (y) a combination of (a), (9), (6), 1, (6), (g) and (6), ( z) a combination of (8), (9), (6), 1, (6), (h) and (6), (aa) a combination of (8), (b), (6), 1, (e), (i) and (c), (bb) Combination of (8), (b), (6), (6), (f) and (c), (cc) (8), (b), (6), (6), (g) and (c), 144087-SP-20091119-1 -40- 201019951 (This) combination of (8), (9), (6), (6), (h) and (c) ' (Shen) (8), (b), (4), (8), (1) and (6), (ff) (8), (9) (k)(8), (b), (k), (9), 1 and (c), (hh)(8), (b), (e), (k) Combination of (6), (8) (8), (b), (6), (k), (d), 1 and (c), Gj) (8), 1 and (c), (kk) (8), 1, (1 Combination of (), (11), (8), 1 and (6),

144087-sp-20〇mi9-l -41 201019951 ο

Where ^^,^,^,^,,, and 丁 and Ding are as defined herein. DETAILED DESCRIPTION The materials and associated techniques and devices described herein will now be described with reference to a particular embodiment. The important properties and ❿ characteristics of the specific embodiments are shown in the structure herein. Although the compositions, compounds, and methods described herein are described in connection with the specific examples, it should be understood that the compositions, compounds, and methods described herein are not limited to such specific embodiments. Instead, the compositions, compounds, and methods described herein are intended to cover alternatives, modifications, and equivalents, and are included in the spirit and scope of the appended claims. In the following description, numerous specific details are set forth to provide a thorough understanding of the compositions, compounds and methods described herein. The compositions, compounds, and methods described herein are contemplated as appropriate without necessarily requiring some or all of such specific details. Described herein are novel semi-synthetic glycopeptides having antibacterial activity. The semi-synthetic glycopeptide described herein is a modification of a natural glycopeptide, or a hydrolysis of a disaccharide moiety of the amino acid of the original glycopeptide to a monosaccharide; Conversion to an amino sugar; on these natural or semi-synthetic backbones, the amino substituents on the amino-substituted sugar moiety are deuterated by certain sulfhydryl groups; and in the backbone The acid moiety on the cyclic ring is converted to a substituted aryl amine of 144087-sp-20091119-1 -42· 201019951. The key reaction is a suitably protected intermediate compound on the guanamine group of the third amino acid aspartate, using RbS〇2C1, RBCOOH, using a coupling reagent, or a RbS〇2_nc〇 group in a base such as triethyl Deuteration in the presence of an amine, or a 7th amino acid of a suitably protected compound, wherein R4 is hydrogen, and NH2_CHRl5_(CH2;)m_NHS()2RB, NHRD_CHRi 5 -(CH2)q -NRE S〇2 Rb or _CHRi 5 (CH2 \ c〇%, in the presence of furfural hydrolysate, Mannich in acetonitrile with water or other suitable organic solvent. Also provides a method for synthesizing the compound containing the compound Pharmaceutical compositions' and methods of using the compounds for treating and/or preventing diseases, especially bacterial infections. Compounds described herein are compounds having a structure selected from the group consisting of: ,

144087-SP-20091119-1 -43 201019951

Wherein ra is selected from the group consisting of a) hydrogen, b) methyl, c) C2 _Ci 2 _ alkyl, and the core and r2 are each independently selected from the group consisting of a) hydrogen, b) Ci- Ci 2 —alkyl 'C) a q 2 alkyl group substituted by one or more substituents selected from the group consisting of (8) halogen, (b) hydroxyl group, (c) CVCu-alkoxy, ( d) Ci-C3 - alkoxy-Ci-C3 - alkoxy" (6) Amino' (f) (ν(:12-alkylamino, (g) Cl-Cl 2 _ II compound amine' (h Alkenyl, 144087-SP-20091119-1 -44- 201019951 (i) alkynyl, 1Ci-C^-thioalkyloxy, d) q-Cu-alkyl substituted by aryl, e) Substituted aryl substituted (^-(:12-alkyl, f) substituted by a heteroaryl tCi-Cu-alkyl, g) substituted by a substituted heteroaryl Cl_Cl2_alkyl, h) naphthenic a group, i) a ring-like group, j) a heterocycloalkyl group, or a heart taken together with the ruler 2 and the atoms to which they are attached, forming a substituted heteroaryl group or a 3-10 membered heterocycloalkyl ring, The case contains one or two heterofunctional groups selected from the group consisting of: -〇-, -NH, -NA-Q-alkyl)-, -N(aryl)-N (aryl A-C6) -alkyl-)- , -N(substituted-aryl-CVC6-alkyl_)_, _N(heteroaryl)-, -N(heteroaryl-Ci-C6_alkyl-)-, -N(substituted-hetero) Square-C!-Cg-Hyun*yl-)_ and -S-0RS(0)n- 'where η is 1 or 2, and the 3-10 membered heterocycloalkyl ring is optionally one or more Substituted by a substituent, the substituents are independently selected from the group consisting of (8) halogen, (b) trans group, (c) -C3 - a gas-burning group, (9) Ci-C3 - a gas-based group - Ci-C3_Entertaining anoxy group '(e) Keto group, 144087-SP-20091119-1 -45· 201019951 (f) Ci-C3 -alkyl group (g) Ci -C3 _ academium, (h) Ci -C3 - alkoxy-C !-C3 - burning base, and

Jr) C(=0)R7, 1) c(=0)CHR8NR9Rl0 ' wherein R8, R9 and R10 are independently selected from the group consisting of: gas, lower alkyl, substituted lower alkyl, aromatic a substituted or substituted aryl group, a heteroaryl group or a substituted heteroaryl group, or a combination of a cardinal and an atom to which they are attached, forming a 3-10 membered heterocyclic alkyl ring, depending on the case Substituted by - or a plurality of substituents 'substituents are independently selected from the group consisting of the following groups (8) ii, (b) hydroxy, (C) CVC3-alkoxy, (d) Q-CV alkoxy-qq-alkane Oxyl, (6) keto, (f) Cl -C3 -alkyl, (g) C! -C3 - dentate, (h) Q-CV alkoxy-q-Cy alkyl; & Groups of the following composition a) hydrogen, b) Α_〇12-alkyl, 144087-sp-20091119-l -46-201019951 C) q-Cu-alkyl substituted by one or more substituents, substituent a group selected from the group consisting of (8) halogen, (b) hydroxyl, (8) q-Cu-alkoxy, (6) Ci-cv alkoxy-Ci-cv alkoxy, (e) amine, (f) CVCu-alkylamine Base, · (g) Cl-Cl 2 _ diacetinyl ' (8) alkenyl, (1) alkynyl, (j) Cl-Cl 2-thio alkoxy ' d) substituted by aryl C i-Cu-alkyl, e) substituted by a substituted aryl group (^-(:12-alkyl, f) substituted by a heteroaryl group, • g) substituted by a substituted heteroaryl group Ci -Cu-alkyl, h) cycloalkyl, : i) cycloalkenyl, ·· j) heterocycloalkyl, k) Cl _Ci 2 _ aminino, 1) amine, m) amino-naphthenic The group is selected from the group consisting of (1) hydrogen, 144087-SP-20091119-1 -47· 201019951 (2) gas; Y is selected from the group consisting of (1) oxygen, (2) Ν &Definitions; The lanthanide is selected from the group consisting of (1)-so2rb, (2) -CORB, (3) -C0NHS02RB; R is selected from the group consisting of (1) hydrogen, (2) cycloalkyl, (3) cycloalkenyl (4) Ci-Ci 2 -alkyl group, substituent (5) Ci_Ci2 alkyl group substituted by one or more substituents selected from the group consisting of (4) halogen, (b) thiol, (c) Α -(:12-alkoxy, (6) CVC3-homolyl alkoxy, (e) -COOR5 'wherein r5 is hydrogen or lower alkyl, and is (f) -C(0)NR5R6, wherein R5 is As defined above, hydrogen or lower alkyl, (g) amine, (h) -NRSR6, where ^ and ^ are as defined above 144087-sp-20 091119-1 -48· 201019951 or & and R6 and their attached atom together, form a 3-10 membered heterocycloalkyl ring, which is optionally substituted by one or more substituents, the substituents are independently selected a group consisting of (1) halogen, (9) hydroxyl, (iv) CVCV alkoxy,

(lv) (VC3-alkoxyoxy, (v) keto, (vi) Ci-C^ 2 -alkyl, (vii) q-Cu haloalkyl, and (viii) (VCV alkoxy Alkyl, (1) aryl, G) substituted aryl,

(k) Heteroaryl, (l) substituted heteroaryl, (m) thiol, (8) Ci-Cl 2 - thioalkyloxy, (6) (:(=0)0&丨' where R! i is Hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, (7)c(=0)NRllRl2' wherein Ru is as defined above, and r port is hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted by 144087-SP-20091119-1 -49- 201019951 ^, pyraryl or substituted heteroaryl, Or the heart and the ^2 and the atoms to which they are attached. The ring is substituted with one or more substituents, and the substituents are independently selected from the following constituents. Group (8) halogen, (b) thiol, (6) CVQ-alkoxy, (6) q-cv alkoxy _Ci_c3_alkoxy, (6) yl, 1Cl -Cl 2 -alkyl, (g) substituted low carbon Alkyl, (h) C1 -Cl 2 haloalkyl, (i) amine, 1 alkylamino, (8) dialkylamino and a) q-cv alkoxy_Cl_Ci2_alkyl, or R and its linkage The oxygen atom is taken together as a halogen; R3 is selected from the group consisting of (1) OH, (2) 1- King Kong Alkylamino, (3) 2-adamantanylamino, 144087-sp-20091119-1 -50- 201019951 (4) 3-amino-1-adamantanylamino, (3) 1-amino-3-adamantanylamino, (6)3 - a lower alkylamino-1-adamantanyl group, (7) 1-lower alkylamino-3-adamantanylamine, (8) an amine group (9) NR! 3 Ri 4, wherein Ri 3 and R 4 are each independently a group selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, cycloalkyl, substituted cycloalkyl, amine lower alkyl, wherein the amine low carbon alkyl amine The base moiety is further unsubstituted or substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, arylaryl, alkoxy, aryloxy, substituted alkoxy and substituted An aryloxy group or &3 together with R!4 and the atoms to which they are attached form a 3_1 membered heterocycloalkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of Group (8) dentate, (b) hydroxy, (c) q-cv alkoxy, (6) oxy _Cl_C3 _ oxy, (6), (f) fen, (g) substituted lower hexane Base, (h) ci -Ci 2 _ morphine, (i) amine group, I44087-sp-20091119 -1 -51- 201019951 1 alkylamino group, (k) dialkylamino group and (l) C1-C3-homoyloxy-Ci-Ci2_alkyl, r4 is selected from the group consisting of the following constituents (1) CH2NH -CHR15-(CH2)m-NHS02RB, where m is from 1 to 6, and R15 is deuterium or lower alkyl, (2) ch2nh-chr15-(ch2)p-conhso2rb, where ρ is from 0 to 6, and R15 Is hydrazine or lower alkyl, (3) CH2NH-CHR15-(CH2)p-COOH, wherein ρ is from 0 to 6, and R15 is hydrazine or lower alkyl, (4) CH2NRD-CHRi5-(CH2)q -NRES02RB, wherein q is 2 to 4, and Ri 5 is H or a lower carbon group, and Rd and Re ' are not -CH2 - ' (3) Η, (6) CH2NHCH2P03H2, (7) an amine lower alkyl group, wherein The amine moiety of the amino lower alkyl group is further substituted by unsubstituted or substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, arylaryl, alkoxy, aryloxy, substituted The alkoxy group and the substituted aryloxy group are substituted, provided that when T is hydrogen, the R4 of the structures II, III and W cannot be selected from the group consisting of hydrazine, CH2NHCH2P03H2, and an amine lower alkane. a group wherein the amine moiety of the amine lower alkyl group is further unsubstituted or substituted Alkyl, alkenyl, cycloalkyl, cycloalkenyl, arylaryl, alkoxy, aryloxy, substituted alkoxy and substituted 144087-SP-20091119-1 -52- 201019951 aryloxy Substituting; RB is selected from the group consisting of a) aryl, b) Ci-C12-alkyl, c) a C1-Ci2-alkyl substituted with one or more substituents, the substituent being selected from the group consisting of (a) ί,

(b) hydroxy, (c) Ci-C12-alkoxy, (d) Q-C3-alkoxyoxy, (6) amine, (f) Q-Cu-amine group, (g) Ci-Ci2 -dialkylamino, (h) alkenyl, 1 alkynyl, 1C1 -Q 2 -thioxyloxy, d) Ci _Ci 2 -alkyl substituted by aryl, e) substituted by substituted aryl iCl_Cl2_alkyl, f) substituted by a heteroaryl group -^-(:12-alkyl, g) substituted by a substituted heteroaryl group, CrCu-alkyl, h) cycloalkyl, i) _ heteroaryl a group, j) heterocycloalkyl, k) an aryl group substituted by one or more substituents selected from the group consisting of 144087-SP-20091119-1 -53* 201019951 column (8) dentate, (b ) hydroxy, (c) <^-〇: 12-alkoxy, (9) q-CV alkoxy-CVQ-decyloxy, (6) amine, 7-amino-qQ-alkoxy (g) Ci_C12-calcined Amine, (9) q-Cu-alkylamino-qQ-alkoxy, (1) Q-Cu-dialkylamino, 1 (ν〇:12-dialkylamino-qQ-alkoxy, (k)alkenyl, (1) alkynyl, (iv) CVCu-thioalkoxy, (8)C--Ci 2 -alkyl, (9)Ci 2 -substituted alkyl, (P) CrCu-alkoxy-morpholinyl, (q) Ci- Cu-院乳基二烧气基胺基, (Γ) q-Cu-烧氧(S) q-Cu-alkoxy_NHC0Ci_C6 alkyl; 1) heteroaryl substituted by one or more substituents selected from the group consisting of (8) halogen, (b) hydroxyl, 144087 -SP-20091119-1 -54- 201019951 (c) (VC12-alkoxy, (d) cvcv alkoxy-Ci-cv alkoxy, (6) amine, (f) amino-CVCV alkoxy ( g) Cl-Cl 2 _Acrylamine ' (h) Ci -Ci 2_Acetylamino _Ci -Cg -Hyun oxy, (i) CVCu-dialkylamino, 1Ci -Ci 2 dioxin ke-Ci-Cg-alkoxy,

(k) alkenyl, (l) alkynyl, (m) q-Cu-thioalkoxy, (8) CVCu-alkyl, (0) Ci-Ci 2 - substituted alkyl,

Rc is each selected from the group consisting of a) hydrogen, b) Ci-Cu-alkyl, c) (^-<:12-alkyl substituted by one or more substituents selected from the group consisting of Group consisting of (8) halogen, (b) hydroxyl, (c) CVC12-alkoxy, (d) Ci-C3 - alkoxy-Ci-C3 - calcined base ' (6) amine, (f) (v < :12-alkylamino, 144087-SP-20091119-1 -55- 201019951 (g) q-Cu-dialkylamino, (h) alkenyl, (i) alkynyl, 1Ci-Ci2-thioalkoxy a group, d) Ci_Ci2_alkyl substituted by an aryl group, e) Ci(i2 alkyl, f) substituted by a substituted aryl group substituted by a heteroaryl group, g) substituted by a substituted heteroaryl group Ci_Ci2_alkyl, h) cycloalkyl, 1) cycloalkenyl, j) heterocycloalkyl, k) C(=0)R7 'where R7 is previously defined, l) C(=0)CHR8NR9R1〇 Wherein r8, r9 and Ri are each independently selected from the group consisting of hydrogen, lower carbon alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl or substituted a heteroaryl group, or RS, is used together with the atoms to which they are attached to form a 31-membered heterocycloalkyl ring, which is optionally treated as one or Substituent substituents 'substituents are independently selected from the group consisting of (8) halogen '(b) hydroxy, (C) Q-C3 -alkoxy, (d) Q-Cr alkoxy-qQ-decyloxy, l440Sl'Sp-2009lll9-l -56- 201019951 (6) keto, (f) cvcv alkyl, (g) q-c3 haloalkyl, (h) CVC3-homolyl_Cl<:3_alkyl; or A pharmaceutically acceptable salt, ester, solvate ammonium salt, stereoisomer, tautomer or prodrug alkylate.

Also provided herein is a pharmaceutical composition comprising a therapeutically effective amount of a compound as defined above in combination with a pharmaceutically acceptable carrier. According to the methods of treatment provided herein, the bacterial infection is in a patient, such as a human or a lower mammal, by administering a therapeutically effective amount to the patient in an amount and for a time as necessary to achieve the desired result. The compound provided in 'is treated or prevented.

In a further aspect, methods and intermediates for the preparation of semi-synthetic glycopeptides of the above formulas j, n, m, ιν and V are provided. In a further embodiment of any of the above structures, ra is methyl and R4 is hydrogen. In another specific embodiment, Ra is hydrogen and & is argon. In another specific embodiment, X is hydrogen and & is hydrogen. In another specific example, X is chaotic and R4 is 虱. In another specific embodiment, RA is methyl' and the heart is CH2NHCH2P〇3 %. In another embodiment, Ra is and R4 is CH2NHCH2 Ρ〇3 Η?. In another embodiment of the invention, 'RA is hydrogen' and R4 is CH2NH-CHR15-(CH2)m_NHS02RB, wherein m is from 1 to 6' and the core 5 is ruthenium or a lower carbon group. In another specific embodiment, Ra is hydrogen ' and ^4 is CH2 NRD -CHR^ 5 -(CH2 )q -NRE s〇2 rb, wherein q is 2 to 4, and core 5 is H or low carbon院基's 〇 〇 % % 表示 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 〇2Rb 'where P is 0 to 6, and R15 is Η or a low-cracking group. In another specific embodiment, Ra is hydrogen and R4 is CH2NH-CHR15-(CH2)p-C〇〇H' wherein 卩 is from 0 to 6' and R15 is oxime or lower alkyl. In another specific embodiment, 'ra is methyl, and R4 is CH2NH-CHR15-(CH2)m-NHS〇2Rb' wherein m is from 1 to 6, and R15 is deuterium or lower alkyl. In another specific embodiment, RA is methyl and R4 is CI^NH-CHRiHCHdp-C〇NHS〇2Rb' wherein P is 〇 to 6, and R15 is fluorene or lower alkyl. In another embodiment, 'Ra is methyl and the heart is CH2NH_CHRi5_(CH2)p_COOH, wherein p is 〇 to 6' and Ri5 is η or lower alkyl. In a further embodiment of any of the foregoing specific examples, R3 is selected from the group consisting of (1) ΟΗ, (2) 1-adamantanyl, (3) 2-adamantanyl, (4) 3-amino-1-adamantane Amino, (3) 1-amino-3-adamantanylamino, (6) 3-lower alkylamino-1-adamantanylamine, (7) 1-lower alkylamino-3-adamantanylamine, (8) amine (9) NRi 3 Ri 4 ' wherein R1 3 and Rl 4 are each independently selected from the group consisting of hydrogen, lower alkyl, substituted lower alkyl, cycloalkyl, substituted naphthenic a group, an amine lower alkyl group, wherein the amine moiety of the amine lower alkyl group is further unsubstituted or substituted alkyl, alkene 144087-SP-20091119-1 • 58- 201019951 base, ring-burning Substituted, cycloalkenyl, arylaryl, alkoxy, aryloxy, substituted alkoxy and substituted aryloxy or r13 together with r14 and the atoms to which they are attached form a 3-10 heterocycle An alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of (4) halogen, (b) trans group, (6) CVCV alkoxy, (6) cvcv alkoxy_Ci _C3_alkoxy, (8) keto, (7) Ci-C12-alkyl, (g) substituted lower alkyl, (8) G-Ci 2 halogen, (1) amine, 1 alkylamino, (k) dioxane Amine and 1Q-cv alkanoyl_Cl_Cl2_alkyl. In a further embodiment 'R3 is OH. In another specific embodiment, R3 is 2-adamantanamine. In another specific embodiment, r3 is a diammonium amino group. In another specific embodiment, R3 is diethylamino. In another specific embodiment, Rs is diammonium ethylamine. In another specific embodiment, R3 is N-methylhexahydroindole. 144087-SP-20091U9-1 -59-201019951 'In a further embodiment of the specific embodiment mentioned in the text, & and 112 are each independently selected from the group of the following components: a) hydrogen, b Ci-C12 • alkyl, C) Ci—Ci 2 —alkyl substituted by — or a plurality of substituents selected from the group consisting of (8) halogen, (b) hydroxyl, (6) C1-Cl 2 alkoxy, (4) (Vcv, oxy-C "C3_^oxy, (6) amine, 1Ci-Ci 2 - acryl, (g) C1-C12-dialkylamino, (h) alkenyl, 1 alkynyl, 1Ci -C12-thiooxooxy, d) Ci_Ci2_alkyl substituted by aryl, e) substituted 2Ci_Cu alkyl by substituted aryl, substituted by heteroaryl (: 丨-(:12-alkane a group, g) Ci_Ci2 alkyl substituted by substituted heteroaryl, h) cycloalkyl, i) cycloalkenyl, J) heterocycloalkyl, or 144087-SO-20091119-1 仏-60 - 201019951 Used together with the heart and the atoms to which they are attached, forming a substituted heteroaryl or a 3-10 membered heterocycloalkyl ring, optionally containing - or two heterofunctional groups selected from the group consisting of: ΝΗ, -ΝΆ-(Ι!6-alkyl)-, -N(aryl )_,_n(aryl<Vc6-alkyl-)_,_N(substituted-aryl_Ci_C6-alkyl+, ~N(heteroaryl)-,·Ν(heteroaryl-Q-Q) -alkyl-)-, _N (substituted-heteroaryl-C:6-alkyl and -S-〇RS(〇)n-, wherein η is 1 or 2' and the 34-membered heterocycloalkane The base ring is optionally substituted by one or more substituents independently selected from the group consisting of (a). Alizarin, (b) hydroxyl, (c) q-CV alkoxy, (d) Q -CV methoxyl_Ci_C3-alkoxy, (6) keto, CO-C3 -alkyl, (g) Q-c3 halogen, (h) Ci-C3 -alkoxy-c3 -alkyl, and k) C(=0)R7, « l) 〇, wherein r8, r9 and o are each independently selected from the group consisting of hydrogen, low carbon alkyl, substituted lower alkyl, aryl, Substituted aryl, heteroaryl or substituted heteroaryl, or 144087-sp-20091119-1 -61 - 201019951 RAR1Q and the atoms to which they are attached, used as a 3-10 member heterocyclic alkyl group a ring, which is optionally substituted with one or more substituents, the substituents being independently selected from the group consisting of (8) dentate, (9) thiol, (c) q-cv alkoxy, (6) alkoxyoxy, (6) 嗣基①q-cv hospital group, (g) Q -C3 burning halo groups, (h) C] -C3- _Cl_c3_ hospital burn-yl group. In a further embodiment of any of the specific embodiments mentioned above, it is hydrogen. In another specific embodiment, the heart is & ^2_alkyl, and ^ is hydrogen. In another embodiment, R1 is C1_C12-alkyl substituted with an aryl or substituted aryl group, and & is hydrogen. In another embodiment, Ri is c(=〇)ciΆ2·alkyl, and R2 is hydrogen. In another specific embodiment, R^CkOX^NHCrCi2.alkyl, and R2 is hydrogen. In another specific embodiment, the core is a C1-C12-alkoxy group substituted with a 2-alkyl group, and R2 is hydrogen. In another specific embodiment, the core is a Cl-C-thioalkoxy group substituted with a Cl_CQ alkyl group, and R2 is hydrogen. In another embodiment, the core is a C1-C12-alkylamine group substituted with an alkyl group and is converted to argon. In a further embodiment of any of the specific examples mentioned in the text, R is selected from the group consisting of: (1) hydrogen, 144087-SP-20091119-1 -62-201019951 (2) cycloalkyl, (3) cycloolefin (4)C--C: 2 -alkyl group, (3) Ci-C! 2 -alkyl group substituted by one or more substituents, the substituent is selected from the group consisting of (4) _, (b) hydroxy, ( C) C! -C! 2 _ alkoxy, (Φ q-cv alkoxy-ever alkoxy, (6)-coor5, where r5 is hydrogen or lower alkyl, (f) -C(0)NR5 & 'Where as defined above, and & is hydrogen or low carbon alkyl, (g) amine group, (h) -NR^6 'where Rs and Re are as defined above, or with heart and their The attached atoms are employed together to form a 3-10 membered heterocycloalkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of the following 3 components (i) dentate, (9) hydroxyl , (iii) Ci-C3 - alkoxy, (iv) CrCV alkoxy-Cl_c3^ oxy, (V) keto, (vi) Cl-C! 2 -alkyl, 144087-sp-20091119-l -63- 201019951 (vii) (ν〇:12_ alkyl, and (viii) CVC3-alkoxy_Ci_Ci2_alkyl, (i) aromatic , 1 substituted aryl, (k) heteroaryl, (l) substituted heteroaryl, 〇tn) fluorenyl, (8) Q -C: 2 - thioalkyloxy, (6) C (= 〇) 〇 Ri 1 , the center i is hydrogen, low carbon yard, substituted lower alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, (7)! R! 2 'where Ri 丨As defined above, and & 2 is hydrogen, lower alkyl, substituted lower alkyl, aryl 'substituted aryl, heteroaryl or substituted heteroaryl, or R" and R12 and The atoms to which they are attached together form a (four) membered heterocycloalkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of (8) halogen, (b) via, (c) Ci-CV alkoxy, (6) Q-Cr alkoxy · Ci_C3_alkoxy, (6) keto, 144087-SP-20091119-1 201019951 (ί) CVCu-alkyl, (g) substituted lower alkane Base, (h) alkyl, 1 amino group ' • G) acrylamine *; (k) dialkylamino group and • (1)C! -C3 - alkoxy-Ci 2 -alkyl group, or R and its linkage The oxygen atoms are taken together as _. In a further embodiment of any of the specific embodiments mentioned above, R is hydrogen. In another specific embodiment, RgCi_Ci2 alkyl. In another specific embodiment, R is q-Cu-alkyl substituted with an aryl or substituted aryl. In another specific embodiment, R is c(=〇)NHCi_Cw alkyl. In another specific embodiment, R is an alkyl group substituted with an aryl group or a substituted aryl group. In another specific embodiment, R is ¢:(=0)0(^-C^2-alkyl. In another specific embodiment, R is heteroaryl: phenyl or substituted heteroaryl Substituting c(=〇)NHCi_Ci 2 alkyl. In any of the further specific embodiments of the specific examples mentioned above, the RB is selected from the group consisting of a) aryl, b) q-Cw alkane a group, c) a q-Cu-alkyl group substituted by one or more substituents selected from the group consisting of 144087-sp-20091119-1 -65- 201019951 (8) halogen, (b) hydroxyl group, (c CVCu-alkoxy, (d) Ci-C3 - alkoxy-Ci-C3 - alkoxy" (6) amine group, (f) CVC12-alkylamino group, (g) Cl-Cl 2 _ II compound Base '(8) alkenyl, (i) alkynyl, 1q-Cu-thioalkoxy, d) q-Cu-alkyl substituted by aryl, e) substituted iCi-Cu-alkane by substituted aryl a group, f) substituted by a heteroaryl group (^-(:12-alkyl, g) substituted by a substituted heteroaryl group of qc^-alkyl, h) cycloalkyl, i) heteroaryl, j a heterocycloalkyl group, k) an aryl group substituted by one or more substituents selected from the group consisting of (8) halogen, (9) hydroxyl group, (c) CVCu-alkoxy group (6) (vc6-alkoxy-CVC6-alkoxy, (6) Amino, 144087-SP-20091119-1 -66-201019951 ω-amino-cvcv alkoxy (g) cvc12-alkylamino, (h) Ci -Ci 2 -Acetylamino-C]_-Cg-calcined base' (i) Ci-Ci 2_diamined amine' 1CVC12-dialkylamino-CVQ-alkoxy, (k) alkenyl, (l) alkynyl, (m) Ci-Ci 2 thiochamolacyl' (8) CVCu-alkyl, 1) heteroaryl substituted by one or more substituents selected from the group consisting of a) spectrin, (b) hydroxy, (c) (VCu-alkoxy, (d) cvq-alkoxy-q-cv alkoxy, (6) amine, (f) amine-CVCV alkoxy , (g) q-Cu-alkylamino, 〇l) Ci -Ci 2 _ acryl group _Ci -C6 - alkoxy ' 1Cl -Cl 2 -diamine amino group' (j) Ci -Ci 2 _ Di-alkali-based _Ci-Cg-alkoxy, (8) alkenyl, (l) alkynyl, (m) Ci-Ci 2 thio-alkoxy' 144087-sp-20091119-1 -67- 201019951 (8)q-Cu -alkyl;

In a further embodiment of any of the specific embodiments mentioned above, the base is burned. In another specific embodiment, % is C!-C! 2 -alkyl substituted with an aryl or aryl substituted aryl group. In another specific embodiment, RB is Ci_Ci2 alkyl substituted with a heteroaryl or substituted heteroaryl. In another specific embodiment, Rb is an aryl group substituted with a Ci_Ci2_alkyl group. In another specific embodiment, Rb is an aryl group substituted by a halogen. In another specific embodiment, RB is a substituted Ci-Cu-alkyl substituted aryl group. In another specific embodiment, RB is a C1_C12 alkyl group substituted with an alkoxy group. In another specific embodiment, RB is a Ci_Ci2-alkyl substituted with a halogen. In another specific embodiment, RB is an aryl group substituted with a Cl_Cl2_alkoxy group. In another specific embodiment, RB is an aryl group substituted with a Cl_C6_alkoxy-Ci_C6-alkoxy group. In another specific embodiment, the aryl group is substituted with an amine group -Ci_c6_alkoxy group. In another specific embodiment, Rb is an aryl group substituted with an alkylamino-q-C6-alkoxy group. In another specific embodiment, Rb is a Ci_Ci2 alkyl substituted with a heteroaryl or substituted heteroaryl. In another embodiment, rb is a heteroaryl substituted with a Cl_Ci2-alkyl. In another specific embodiment, rb is a heteroaryl group substituted with a cyclin. In two other specific embodiments, rb is a heteroaryl group substituted with a Cl_Ci2-alkyl group. In another specific embodiment, RB is a heteroaryl group substituted with a substituted q_cl2_alkyl group. In another embodiment, RB is a heteroaryl group substituted with a C1_C12•houseoxy group. In another embodiment, Rb is a heteroaryl group substituted with a gas-based group -CVQ-alkoxy group. In another specific embodiment, % is a heteroaryl group substituted with an amino-q-C6-alkoxy group. In another embodiment, B 144087-sp-20091119-l-68-201019951, Rb is a heteroaryl group substituted by ci_cu-alkylamino-q-Cf alkoxy. In a further embodiment of any of the foregoing specific embodiments, the Rc systems are each selected from the group consisting of a) hydrogen, ; b) Cl-Q 2 -alkyl, c) • one or more Substituent substituted q_C12_alkyl, the substituent is selected from the group consisting of (a) _, (b) hydroxy, (C) Cl-C12-homolyl, (9) q-cv alkoxy _Ci_C3_ Oxyl, (6) amine, (f) (Vc12-alkylamino, (8) C1_C12-dialkylamino, 〇1) alkenyl, 1 alkynyl, : d) 1C1_C12-thioalkoxy, substituted by aryl Cl_cl2_alkyl, .e) Ci _Ci 2 alkyl substituted by substituted aryl, f) substituted by heteroaryl (^-(:12-alkyl, g) substituted by substituted heteroaryl C1_C12_alkyl, h) cycloalkyl, i) cycloalkenyl, j) heterocycloalkyl, 144087-SP-20091119-1 • 69· 201019951 k) C(=0)R7 'where R7 is previously By definition, l) ChCOCHRsN^Ri〇, wherein R8, R9 and R! are each independently selected from the group consisting of hydrogen, low carbon alkyl, substituted low carbon, aryl, substituted Aryl, heteroaryl or substituted heteroaryl, or & R1 0 is used together with the atoms to which they are attached to form a 3-10 membered heterocycloalkyl ring 'which is optionally substituted with one or more substituents'. The substituents are independently selected from the group consisting of (8) iS, (b) Hydroxy, (6) q-cv, oxy, (6) q-cv alkoxy _Ci_C3_alkoxy (6) yl, (f) C--C3 - alkyl, (8) q-c3 halogen,

(h) q-Cr alkoxy _Ci_c3_alkyl. In the specific embodiment of the specific embodiment mentioned in the text,

Rc is 虱. In the other item and one specific ^ / , is ^12 · burning base. In c _c 歹1 , & is substituted by an aryl or substituted aryl group. In another embodiment, Rc is substituted by a heteroaryl or substituted heteroaryl group. Replace it. r μ $ item in the specific embodiment

Rc is C(, vc12_alkyl. In the item: in the embodiment, in the specific embodiment, Rr 144087-sp-20091119-1 -70-201019951 CX^CHaNHCVCV hospital base. In another specific In the examples, & is Ci-C 2-alkyl substituted CrCu-alkoxy. In another specific embodiment, 11 <: qC^2-alkyl substituted q-Cu-thio Alkoxy. In another embodiment, 'alkyl substituted Cl_Cl2• alkylamino. In a further embodiment of any of the above structures, γ is oxygen and the heart is hydrogen. In another embodiment In the other embodiment, 'Y is oxygen, and r4 is CH2NHCH2P〇3H2. In another specific embodiment, Y is NH and the heart is CH2NHCH2P 〇3H2. In a further embodiment, T is -S02RB and R4 is hydrogen. In another specific embodiment, T is -CORB and R4 is hydrogen. In another embodiment, 'T is -CONHS〇2 RB, and R4 is hydrogen. In another specific embodiment, T is -S02RB' and R4 is CH2NHCH2P〇3H2. In another specific embodiment, T is -CORB and R4 is CH2NHCH2P 〇3H 2. In another embodiment, 'T is -C0NHS02RB, and r4 is ch2NHCH2COOH. In another specific embodiment, τ is -so2rb and the heart is CH2NHCH2COOH. In another specific embodiment, T is -CORb, and R4 is CH2NHCH2COOH. In another specific embodiment, τ is _conhso2rb, and R4 is CH2NHCH2COOH. In any of the specific embodiments of any of the aforementioned specific examples, Ri is hydrogen. And R 2 is COCHRs NHRi6, wherein Ri 6 is a substituted aryl group, and Rs is as defined above. In another embodiment, 'is providing formulas i, ii for the synthesis of an antibacterial agent of formula IV, Iii, iv intermediate compound 'and wherein Ra is argon or methyl, X is gas or hydrogen, and R4 is hydrogen, CH2NHCH2P〇3 h2 or amine low carbon yard, 144087-SP-20091119-1 •71 201019951 Omino or 2-adamantylamino. Definitions Unless otherwise indicated, the terms used herein shall be given their ordinary meaning as understood by those skilled in the art. The term "alkyl" is used herein. , derived from the inclusion of - by removing a single hydrogen atom A saturated, linear or branched chain hydrocarbon group of a carbon atom of a carbon atom between ten. The substituted surface group-word used herein refers to _, two or three by dentate, alkoxy An alkyl group substituted with a group consisting of an amino group, an amine group, an alkylamino group, a dialkylamino group, a hydroxyl group, an aryl 'heteroaryl group, an alkenyl group or an alkynyl group. As used herein, the term "alkenyl" refers to an unsaturated, straight or branched chain derived from a hydrocarbon moiety containing two or twenty carbon atoms by the removal of a single hydrogen atom. Chain hydrocarbon group. As used herein, a ring-based group, a word, is derived from a single or double ring saturated with three or twenty carbon atoms by removing a single gas atom. The monovalent group of a carbocyclic compound. The term "substituted cycloalkyl" as used herein means a radical, a di- or two-membered, alkoxy, amino, alkylamino, dialkylamino, The hydroxy:; group substituted by a group consisting of a heteroaryl group, an alkenyl group or an alkynyl group is used herein, and the term "ring dilute base" refers to the removal of a hydrogen atom by ^1. a monovalent group derived from a monocyclic or bicyclic unsaturated ring-breaking compound having between three and twenty carbon atoms. As used herein, "Cl-C3_alkyl," 'Ci_C6_alkyl "and"Ci_c broad-based terminology refers to a group derived from a hydrocarbon moiety by the removal of a single hydrogen atom: 144087-sp-20091119-l -72- 201019951 a saturated, linear or branched hydrocarbon group containing one, three, one and six and one and twelve carbon atoms. Examples of Ci_c3_alkyl include methyl, ethyl, propyl and isopropyl. Examples of the q-C6-alkyl group include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, and n-hexyl ° C! -C Examples of 2_alkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n-hexyl, n-heptyl, n-octyl Base, n-decyl, n-decyl, n-undecyl and n-aryl. The term low carbon alkyl as used herein refers to a Cl-Cl 2 -alkyl group as defined above. The term "substituted lower alkyl" as used herein refers to one, two or three of dentate, alkoxy, amine, alkylamino, dialkylamino, hydroxy, aryl, heteroaryl. a group consisting of a group consisting of an alkenyl group or an alkynyl group substituted with a Cl_Cl2 alkyl group. The term "匸3々2-cycloalkyl" means derived from a monocyclic or bicyclic ring by removal of a single hydrogen atom. Monovalent base I example package for saturated carbocyclic compounds % propyl, cyclobutyl, cyclopentyl, S hexyl, bicyclo[2 21]heptyl and bicyclo[2.2.2]octyl. As used herein, χ〆3·alkoxy", The term "Ci_C6·alkoxy" means a Cl-c3_alkyl group and a Ci_C6•alkyl group as defined above, which are bonded to a parent molecular moiety through an oxygen atom. Examples of the Ci_Q nozzleoxy group include, but are not limited to, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a n-butoxy group, a tert-butenyl group, a neopentyl group, and a n-hexyloxy group. As used herein, the term "low carbon amine group" refers to a Cl-C12-alkyl group as defined above which is attached to a parent molecular moiety through a nitrogen atom. Low 144087-SP-20091119-1 • 73-201019951 Examples of carboalkylamine groups include, but are not limited to, methylamino, dimethylamino, ethylamino, monoethylamino, propylamino and decylamino groups. The term 'keto group' denotes a group wherein two hydrogen atoms on a single carbon atom in an alkyl group as defined above are replaced by a single oxygen atom (ie, a carbonyl group). "Aryl group" as used herein. , the term, refers to a mono- or bicyclic carbocyclic ring system having one or two aromatic rings, including but not limited to phenyl, fluorenyl, tetrahydroindenyl, hydroindole, fluorenyl, etc. And, as the case may be unsubstituted or substituted by one, two or three substituents (including bicyclic aryl), the substituents are independently selected from lower alkyl, substituted lower alkyl, haloalkyl , Ci_Ci2 alkoxy, thioalkoxy, q-Q2-thioalkoxy, aryloxy, amine, alkylamino, dialkylamino, decylamino, cyano, hydroxy, dentate , mercapto, nitro, carboxaldehyde, carboxyl, alkoxycarbonyl and carboguanamine. Further, the substituted aryl group includes a tetrafluorophenyl group and a pentafluorophenyl group. The term "substituted aryl" as used herein, refers to a mono- or bicyclic carbocyclic ring system having one or two aromatic rings, including but not limited to phenyl, fluorenyl, tetrahydrogen. Amidino, hydroquinone, fluorenyl, substituted by a 'two or three substituents (including bicyclic aryl), the substituents are independently selected from lower alkyl, substituted lower alkyl,! |alkyl, Ci_Ci2_alkoxy, thioalkoxy, q-Cu-thioalkoxy, alkoxyalkylalkoxy, aryloxy, amine, aminoalkyl, aminoalkyl Alkoxy, alkylamino, alkylaminoalkyl, alkylaminoalkylalkoxy, dialkylamino, dialkylaminoalkyl, dialkylaminoalkylalkoxy, decylamino, Cyano, hydroxy, _, thiol, nitro, carboxaldehyde, thiol, alkoxy, aryl, heteroaryl, heteroaryl and carboguanamine. This 144087-sp-20091119-1 •74·201019951, the substituted aryl group includes a tetrafluorophenyl group and a pentafluorophenyl group. As used herein, the term "aromatic base" refers to an aryl group as defined above which is attached to a parent molecular moiety via a guanyl group wherein the alkyl group has from one to twelve carbon atoms. The term "substituted aralkyl" as used herein, refers to a substituted aryl group as defined above which is attached to a parent molecular moiety through a pendant group, wherein the alkyl group has One to twelve carbon atoms.

The term "alkylaryl" as used herein, refers to an alkyl group as defined above which is attached to the parent molecular moiety through an aryl group. As used herein, "dentate," and "function" terms refer to atoms selected from the group consisting of fluorine, chlorine, bromine, and iodine. "alkylamino" means a group having the structure -NHR, wherein R1 is an alkyl group as defined herein. Examples of the alkylamino group include a methylamino group, an ethylamino group, an isopropylamine group and the like. The term 'dialkylamino" refers to a group having the structure _NHR, R, wherein R, and R" are independently selected from alkyl as defined above. In addition, R, together with R" The case is -(CH2)k- 'wherein k is an integer of 2 to 6. Examples of the dialkylamino group include a diammonium group, a diethylamino group, a mercaptopropylamine group, a hexahydropyridyl group, etc. "haloalkane The term "base" means an alkyl group as defined above, having one, two or three halogen atoms attached thereto, and exemplified by groups such as a gas methyl group, > odoryl ethyl group, Tris- 1 fluorenyl and the like. '• Alkoxycarbonyl π — The word is represented by an ester group; that is, an alkoxy group which is bonded to a part of a parent molecular group through a carbonyl group, such as a methoxycarbonyl group, an ethoxycarbonyl group or the like. The term "hyun" is used to refer to a previously defined alkyl group which is attached to a parent molecular moiety through a sulfur atom 144087-SP-20091119-1 -75- 201019951. As used herein, "slow acid" The word 'system' is a CHO group. The term "rebel" as used herein, refers to a radical of the formula _c〇2H. The term "carboxyguanamine" as used herein refers to a radical of the formula wherein R and R are independently selected from hydrogen. , the base, the substituted low-carbon base, or R, and R"- as the case is _ (CH Shi, where ... is an integer. The term "aryl" used in this article refers to a cyclic or bicyclic aromatic group having five to ten electrical atoms in each ring, wherein at least one atom of the cyclic or bicyclic ring is selected from the group consisting of s, hydrazine and N optionally substituted; , or - two ring atoms are other heteroatoms' independently selected from the optionally substituted S'OM; and the (iv) atom is carbon' which is bonded to the rest of the molecule via any ring atom, such as _ "(4) base, mouth bite base, (four) base "bis, imipenyl" sialyl, ten-seat, hetero-s-sitting, sulphate, thiophenyl, base, base, diss Base, peak bite, etc. As used herein, the term "substituted hydrazine I" is used to mean a cyclic or bicyclic aromatic group, having five to + one aid store 7 Two to ten The atom is in each ring, wherein at least the -(iv) sub-system of the cyclic or bicyclic ring is selected from the optionally substituted 5' ◦ and N; zero or two ring atoms are other heteroatoms, independently selected from the case Substituted S, hydrazine and N; and the remaining ring atoms are carbon, the group is bonded to the rest of the molecule via any ring atom, such as a bite group, a base, a thiol group, (4) base, "base, ^ base, iso-oxazolyl moxadiazolyl, thiophenyl 'furanyl,: phenyl group: hetero-linyl, philophilic and similar groups, one, two or three Substituting 144087-sp-20091119-1 -76-201019951 base substitution, the substituents are independently selected from lower alkyl, substituted lower alkyl, haloalkyl, q-Cu-alkoxy, thioalkoxy , Ci_Ci2_thioalkoxy, alkoxyalkylalkoxy, aryloxy, amine, aminoalkyl, aminoalkylalkoxy, acrylamine, alkylaminoalkyl, alkylamino Alkyl alkoxy, dialkylamino, dialkylaminoalkyl, dialkylaminoalkylalkyl fluorenyl, decylamino, cyano, hydroxy, hydrazine fluorenyl, nitro, carboxaldehyde, carboxyl Alkoxycarbonyl, aryl Heteroaryl, heterocyclic aryl and carboguanamine. As used herein, the term 'heterocycloalkyl" refers to a non-aromatic partially unsaturated or fully fully saturated 3- to 10-membered ring system. It comprises a monocyclic ring of 3 to 8 atoms in size, and a bi- or tri-cyclic ring system comprising an aromatic six-membered aryl or heteroaryl ring fused to a non-aromatic ring. The cycloalkyl ring includes those having a hetero atom independently selected from the group consisting of oxygen, sulfur, and nitrogen, wherein the nitrogen and sulfur heteroatoms are optionally oxidized, and the nitrogen heteroatoms are optionally quaternized. Representative heterocycloalkyl rings Including but not limited to tetrahydropyrrolyl, dihydropyrazolyl, tetrahydropyrazolyl, dihydroimidazolyl, tetrahydroimidazolyl, hexahydropyridyl, hexahydropyrrole, tetrahydrocarbazolyl, isotetra Hydrogen, oxazolyl, morpholinyl, oxazolidinyl, iso-p-s-decyl, and tetrahydrofuranyl. As used herein, the term 'heteroaralkyl" refers to a heteroaryl group as defined above which is attached to the parent molecular moiety through an alkylene group wherein the alkylene group has from one to four carbon atoms. "protecting group" means a group that is readily removable to protect a functional group, such as a hydroxyl group, a ketone or an amine, to prevent unwanted reactions during the synthetic procedure, and is selectively removable. Examples of such protecting groups are known, see, for example, TH Greene and RGM. Wuts, Protective Groups for Organic Synthesis, 2nd Edition, j〇hn 144087-sp-20091119-1 -77· 201019951 WHey & Sons, New York (Gu). Examples of sulfhydryl-protecting groups include, but are not limited to, methylthiomethyl, tert-dimethylhydrazine, tributyl butyl diphenyl sulfonium, such as methoxymethyl, and vinegar Including acetamyl, benzhydryl and the like. Examples of ketone protecting groups include, but are not limited to, ketals, anthraquinones, hydrazine-substituted substituted oligosaccharides such as fluorene-grain, 0-phenylthioindolyl M isopropoxycyclohexyl. Examples of amine protecting groups include, but are not limited to, tris-butoxycarbonyl (Boc) and benzyloxycarbonyl (Cbz). The term "protected hydroxy" refers to a radical protected by a hydroxy protecting group as defined above. Amino acid term refers to an amino acid having D or L stereochemistry and also refers to synthetic, unnatural amino acids. a side chain other than those found in the 20 common amino acids. Non-natural amino acids are commercially available or, as the case may be, based on 5,488,131 and references therein. Amino acid systems The situation is further substituted to include modifications to its amine, slow or side chain groups. These modifications include many protecting groups commonly used in peptide synthesis (TH Greene and pGM Wuts, Protected Groups for Organic Synthesis, 2nd Edition) , J〇hn (4) &SQns> New Y〇rk? 1991). As used herein, substituted heteroaryl, the term refers to a heteroaryl group as defined herein, via Cl, Br , F, I, OH, CN, Ci-Cu-alkyl, q-Cu-alkoxy, Ci_Ci2_alkoxy, arylalkyl, thioalkyl, amine, alkylamine substituted by aryl , dialkylamino, sulfhydryl, nitro, carboxaldehyde, sulphonyl, oxyalkyloxy and decylamine independently substituted one, two or three nitrogen atoms Further, any substituent is optionally an aryl group, a heteroaryl group or a heterocycloalkyl group. 144087-SP-20091119-1 -78-201019951 "'Substituted heterocyclic ring as used herein. The term "alkyl" refers to a heterocycloalkyl group as defined herein by substituting iCi with Cl, Br, F, I, 〇H, CN, alkyl, Ci-C!2-alkoxy, aryl -Cu-alkylhydrazine, dentate, thioalkyl, amine, alkylamino, dialkylamino, sulfhydryl, decyl, carboxaldehyde, carboxyl, alkoxycarbonyl and carboguanamine are independently substituted thereon —, two hydrogen atoms are replaced by two hydrogen atoms. Further, any one of the substituents is optionally an aryl group, a heteroaryl group or a heterocycloalkyl group.

The term "stereoisomer" as used herein refers to any of two forms of a compound having the same molecular formula and having its constituent atoms joined in the same order, but if its atoms are surrounded in space. Asymmetric centers have different arrangements. If an asymmetric center is present in the compound, the compounds described herein include various stereoisomers and mixtures thereof unless otherwise indicated. It is pointed out that otherwise it is intended that the mixture of stereospecific orientations or the specified or undetermined individual isomers are present. The "tautomers" used herein are intended to exhibit two chemical compounds of the tautomeric phenomenon. Any of a variety of forms, the phenomenon being the balance of chemical compounds by proton transfer in the presence of a mixture of two interconverting isomers. The keto group and the dilute alcohol form of the m-based compound are tautomeric An example of a substance which can be converted into each other by a resonance-anhydride anion and a dilute alkoxide ion in the presence of a trace amount of acid. The term salt, which is used, refers to such salts, which are within the scope of safe and medical judgment, and are suitable for joints with humans and lower animals without undue toxicity, irritation, and allergic return. Rational 144087-sp-20091119-1 -79- 201019951 , for example, SM Berge et al., in detail in the Journal of Pharmaceutical Sciences, 66. 1-19 (1977), pharmaceutically acceptable salts, for this project In this context, reference is made to the fourth salt system during the final isolation of the compound described herein, or separately by reacting the free state functional group with a suitable organic acid. Examples of non-toxic acid addition salts are salts formed by amine groups and inorganic acids such as hydrochloric acid, guanidine bromate, phosphoric acid, sulfuric acid and peroxyacid, or salts formed with organic acids, organic acids For example, acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid, or by other methods described, such as ion exchange. Other pharmaceutically acceptable salts include adipate, seaweed Acid salt, ascorbic acid Salt, aspartate, besylate, benzoate, acid sulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentane propionate, Digluconate, dodecyl sulfate, ethane acid salt, citrate t-butylate, glucoheptonate, glycerol phosphate, gluconate, hemisulfate, heptanoate, Hexanoate, hydroiodide, 2-carbyl-benzine, lactic acid bioacid, lactate, laurate, lauryl sulfate, malate, maleate, propylene Acid salt, methane sulfonate, 2-anthracene sulfonate, nicotinic acid salt, nitrate, oleate, oxalate, palmitate, bis-theophylline, pectin acetate, persulphate , 3-phenylpropionate, phosphate, picrate, tridecyl acetate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluene Acid salt, undecanoate, valerate, and the like. Representative alkali metal or soil test metal salts include sodium, chain, oblique, mother, town, and the like. Where appropriate, other pharmaceutically acceptable salts include non-toxic 144087-SP-20091119-1 -80·201019951 ammonium, tetra (10) and amine cations formed using counterions, such as self-roots, hydroxides , carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate and aryl sulfonate. The term refers to esters which are hydrolyzed in vivo, pharmaceutically acceptable esters and include those which decompose in the human body leaving the parent compound or its salt. Suitable acetoxy groups include, for example, those derived from pharmaceutically acceptable aliphatic (IV) classes, particularly alkanoic acids, enoic acids, naphthenic acids and alkanoic acids, wherein each alkyl or alkenyl moiety group advantageously has no More than 6 carbon atoms. Representative examples of specific esters include, but are not limited to, phthalate esters, acetate 'propionates, butyrates, acrylates, and ethyl succinates. The term "solvate" as used herein, refers to a compound formed by solvation cooperation, which is a combination of a solvent molecule and a molecule or ion of a solute comprised of a compound described herein. "The term pharmaceutically acceptable solvate refers to these solvates, which are within the scope of safe and reliable medical judgment and are suitable for contact with tissues of humans and lover animals without undue Irritating, allergic responses, etc., with a reasonable benefit/risk ratio. As used herein, the term "strandyl quaternary ammonium salt" refers to a compound formed by the alkylation of a nitrogen atom of a primary, secondary or tertiary amine with a calcined dentate. Act to form an alkyl quaternary ammonium. "Pharmaceutically acceptable prodrug, the term refers to the prodrug of a compound described herein, which is within the scope of safe and reliable medical judgment and is suitable for contact with tissues of humans and lower animals, without Improper toxicity, irritation, allergic response, etc., along with a reasonable benefit/risk ratio, and for its intended use, and where possible, for the compounds 144087-sp-20〇91119-l described herein • The zwitterionic form of 81 - 201019951. The term "prodrug" refers to a compound that will undergo transformation in vivo to produce a parent compound of the above formula', e.g., via hydrolysis in blood. Full discussion was provided by T. Higuchi and V. Stella, Prodrugs as a new transport system, Volume 14 of the ACS Collection, and Bioreversible Carriers in Drug Design, edited by Edwafd B. R〇che, The American Medical Association and Pergamon Press, 1987, 'for this project, both of which are incorporated herein by reference. Synthetic Methods The synthesis of the compounds described herein is broadly described below. The compounds described herein are prepared, for example, by chemical modification of the compound A, the compound b, the compound η, and the compound C skeleton. Specifically, the semi-synthetic glycopeptides described herein are prepared by chemically modifying a compound A, a compound β, a compound hydrazine, and a compound c or a glycopeptide according to the following manner. Produced to subject the original glycopeptide to hydrolysis in an acidic medium such that the disaccharide moiety of the amino acid-4 of the original glycopeptide obtains a monosaccharide; the amine functional group is a second-butoxycarbonyl group, a benzyloxy group Protection of a carbonyl group, an allyloxycarbonyl group or a 9-yloxycarbonyl group; the acid moiety on the macrocyclic ring of the backbone is converted to a certain substituted amide; in the third amino acid The appropriate intermediate compound on the guanamine of the aspartate, using Rb s〇2 C1, Rb C00H, using a coupling reagent, or a rb S〇2_NCO group, in the presence of triethylamine , and the removal of the protection base. In some embodiments, if the amine functional group on the monosaccharide is converted to a monosaccharide derivative, the amine group on the amine group is substituted on the amino group. Substituents, with some sulfhydryl groups; amine functional groups by the third -butoxycarbonyl, 芊144087-sp-20091119-1 -82· 201019951

Protection of oxycarbonyl, allyloxycarbonyl or 9-fluorenylmethoxycarbonyl; the acid moiety on the macrocyclic ring of these backbones is converted to certain substituted amides, and the compound is isocyanate Processing. The compounds described herein are, for example, made in such a way that the aminoglycan moiety of the functionalized or unfunctionalized glycopeptide from the above backbone, together with the appropriate thiol and/or amine group, Coupling under guanamine forming conditions, and converting the acid moiety on the macrocyclic ring of the formed glycopeptide derivative to certain substituted guanamines; or a combination of the following, on the backbone, in the amine a substituent on a group of a sugar-substituted moiety, modified by alkylation of a certain alkyl group, or an amine group substituent on the amino group of the amine-substituted sugar moiety, The oximation of the amide, guanamine or s-amino acid or its derivatives is modified, and the acid moiety on the macrocyclic ring of the backbone is converted to certain substituted amines. In another series, the compounds described herein are made, for example, by chemical modification of the compound A, the compound B, the compound oxime and the compound C skeleton. Specifically, the semi-synthetic glycopeptides described herein are prepared in such a manner that the chemical modification of Compound A, Compound B, Compound Η and Compound C or a monosaccharide related to a glycopeptide is carried out in the following manner Produced 'to make the original glycopeptide hydrolyzed in an acidic medium' to obtain a monosaccharide moiety of the amino sugar group of the amino acid of the original glycopeptide; the amine functional group by the third-butoxycarbonyl group, the benzyloxy group Protection of carbonyl, allyloxycarbonyl or 9-fluorenylmethoxycarbonyl; for the 7th amino acid of a suitably protected compound, the center is hydrogen ', NHRD-CHR15-(CH2)q-NRES02RB or NH2-CHR15 -(CH2)p-C0NHS02RB 'Mannich reaction in acetonitrile with water or other suitable organic solvent in the presence of an aqueous brewing solution, and removal of the protecting group. In some embodiments, the synthesis of the compound 144087-SP-20091119-1 -83-201019951 also involves the use of protecting or blocking groups to maximize yield, minimize undesirable by-products, or Improve simple purification. Specifically, the semi-synthetic glycopeptides of the compounds described herein are prepared, for example, by modifying the compound A, the compound B, the compound oxime, and the compound to form a skeleton. The glycopeptide starting material is optionally unsubstituted or substituted on the 7th amino acid at the 4 position of the phenyl ring by CH2NHCH2% η2 or an amino lower alkyl group as defined herein. Compound A, Compound β, Compound η or Compound c, wherein the 7th amino acid at the 4' position of the phenyl ring is replaced by hydrogen, CH2NHcH2p or an amine based low carbon wire as defined herein, with an acid choice Sexual hydrolysis, the early cool intermediates. , - generally speaking, the compound of formula w described herein is modified by

- A is hydrogen or sulfhydryl 'X is gas or gas, or alkoxy, 144087-SP-20091119-1 * 84 - 201019951 2-Agonated amine or low carbon amine group' as defined herein, heart is Hydrogen or suitably protected CH2NHCH2P〇3H2 or Boc-amino low carbon alkyl, as defined herein, by a technique selected from the group consisting of: (8) 9-fluorenylmethoxycarbonyl (Fmoc) or third - Butoxycarbonyl (B〇c) _ or other suitable nitrogen protecting group to protect the amine group. (b) using a tertiary amino group of the third amino acid aspartate, using a coupling reagent for RbS〇2C1, Rb COOH', or a Rb s〇2_nc〇 group, in the presence of a base such as triethylamine (6) removing the protecting group of the amine group. The b〇c protecting group is removed with a mild acid such as difluoroacetic acid, and the Fmoc group is removed as a test such as diethylamine or the like. (6) If R3 is an alkoxy group, the alkoxy group is removed by mild or acid hydrolysis to obtain an acid-lowering derivative, (6) the azide functional group is reduced to an amine, (f) the monosaccharide mono-level alcohol or An amine group substituent on the amine φ group of the fourth amino acid of the compound, having the structure RJ (wherein J is a halogen), & -J (where J is a halogen), r2_j (wherein An alkyl halide wherein J is a halogen or RC-J (wherein J is a halogen); alkylation of the compound (g) an amine-substituted sugar moiety of a monosaccharide or a fourth amino acid of the compound The amino group substituent on the group is deuterated by a thiol group having the structure c(=o)r7, (8) the monosaccharide of the monosaccharide or the amino group-substituted sugar moiety of the fourth amino acid of the compound The amine substituent 'is deuterated with a thiol group having a knot 144087-SP-20091119-1 -85- 201019951 C(=0)CHR8 NR9 Ri ,, (i) an amine of the fourth amino acid of the compound The amino group substituent on the sugar moiety is reacted with an aldehyde or a ketone, followed by reductive amination of the imine formed, 1 by the acid moiety on the macrocyclic ring of the compound Conversion by a substituted decylamine as defined by R3, (k) reaction with a phosgene of a monosaccharide moiety or a primary amine of a tetrasaccharide moiety of the fourth amino acid of the compound with an adjacent hydroxyl group, 1 for the compound 7Amino acid, wherein R4 is hydrogen, and NH2-CHR15-(CH2)m-NHS02RB, NHRD-CHR15-(CH2)q-NRE S02 RB or NH2-CHRi 5 -(CH2)p-C0NHS02 RB, in formaldehyde Mannich reaction in acetonitrile with water or other suitable organic solvent in the presence of an aqueous solution, (m) a combination of (a), (b) and (c), a combination of (8) (8), (b), (c) and (6), (6) (8) Combination of (b), (4), 1 and (6), (p) a combination of (8), (b), (f) and (c), (q) a combination of (8), (9), (g) and (c), ( r) a combination of (8), (b), (h) and (c), (s) a combination of (a), (b), (i) and (c), (t) (8), (b), (e) Combination of (c), (8) a combination of (a), (b), (6), (d) and (6), (v) a combination of (8), (b), (6), 1, (4) and (c), (w ) a combination of (a), (b), (6), (6) and (c), 144087-SP-20091119-1 -86- 201019951 (8) (8), (9), (d), 1, (6), (f) and (c) group , (y) a combination of (8), (b), (d), (j), (e), (g) and (6), (z) (8), (b), (6), 1, (6), 〇ι) and c) combination, (aa) (8), (b), (6), 1, (e), (i) and (c), (bb) (8), (b), (d), (e), a combination of f) and (c), a combination of (cc)(8), (b), (d), (e), (g) and (c), (dd)(8), (b), (d), (6) , combinations of (h) and (c), combinations of (ee)(8), (b), (d), (e), (i) and (c), (ff)(4), (9), (k) and c) combination, (gg) combination of (8), (9), (k), (6), 1 and (c), (hh) combination of (8), (b), (6), (k) and (c), (8) (8), ( b), a combination of (6), (k), (6), 1 and (c), a combination of (jj)(4), (1) and (6), a combination of (kk)(8), 1, (1) and (8), (8)1, (a) a combination of (1) and (c) to form a compound having a chemical formula selected from the group consisting of:

144087-SP-20091119-1 -87 201019951

In the corps, R p ' "^, ^, {^, ^, 丫 and 丁 are as defined herein. In particular, the semi-synthetic glycopeptides described in the article are modified by the θ a , made into a total of human plate, compound Η or compound C skeleton. These natural sugars from ^ ^ & your substance D is unsubstituted as appropriate, or ch2nhch2p 〇 3h < The substitution of an amino group of a lower alkyl group is introduced, for example, via a Mannich reaction in which the glycopeptide is treated with an amine and a methacrylate under experimental conditions (for example, as in the Journal of Antibiotics, Vol. 5, No. 6, pp. 509-513. The pharmaceutical compositions described herein comprise a therapeutically effective amount of a compound described herein, formulated together with - or a plurality of pharmaceutically acceptable carriers. As used herein, the term "pharmaceutical" means "shouldering, inert solid, semi-solid or liquid filling, Dan 7r>t, thinner, rubberized Any kind of auxiliaries that are far from any type of material. A 144087-sp-20091119-1 •88· 201019951 Examples of gum oils are sugars, such as lactose, glucose and sucrose; starches, such as corn house powder and potato starch; cellulose and its derivatives, such as slow A Cellulose sodium, ethyl cellulose and cellulose acetate; powdered sassafras malt; gelatin; talc; excipients, such as cocoa butter and suppository wax oils such as peanuts, cottonseed oil; safflower oil; Sesame oil; olive corn oil and soybean oil; glycols; such as propylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffer, such as magnesium hydroxide and aluminum hydroxide; sea bream; Pyrogen-containing water; isotonic saline; Ringer's solution ethanol and phosphate buffer solution, and other non-toxic compatible lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating Additives, sweetening, flavoring and aromaing agents, preservatives and antioxidants are also present in the composition, depending on the judgment of the formulator. The pharmaceutical compositions described herein are in the form of wart. , parenteral, intracisternal, vaginal, intra-abdominal, topical (eg by powder, ointment or drops), cheeks to humans and other animals, or for oral or nasal sprays Or a liquid aerosol or dry powder formulation for inhalation. A liquid dosage form for oral administration, including pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and granules. 9 In addition to active compounds 'Liquid dosage forms contain inert diluents, such as water or: other solvents, solubilizers and emulsifiers, such as ethanol, isopropyl #, ethyl acetate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 13 - Butanediol, monomethylamine, oils (especially cottonseed, groundnut, glutinous rice, germ, olive ramie and sesame oil), glycerin, hydrogen bite, glycerol, and sputum The fatty acid δ of sugar, and a mixture thereof. In addition to the inert diluent, the 144087-sp-20091119-l •89· 201019951 group also contains adjuvants, sweetening, flavoring and fragrances, as appropriate. "T injection preparations, such as sterile aqueous suspensions, are formulated with a == or wetting agent in combination with a suspending agent. Sterile injectable preparations are as follows: = injectable solutions, suspensions or emulsions, in non-toxic non-menstrual. The acceptable medium used in the case is as follows: in the middle of the solution, the bismuth and the bathing agent are water, U.S.P.= solution and isotonic chlorinated steel solution. Further, the volatile oil acts as a solvent or a suspension medium. For this project, feedstock 5 = volatile oils are used as appropriate, including synthetic mono- or diglycerides 1 , 'deuterium fatty acids' such as oleic acid, which are used in the preparation of injectables. Injectable formulations are sterilized, for example by borrowing, or by incorporation, by filtration through the bacteria that retain the bacteria by incorporation of a sterilizing agent in the form of a sterile solid composition = before being dissolved or dispersed Sterile water or other sterile injectable vehicles are used to prolong the action of the drug, and it is generally desirable to slow the absorption of the drug from the skin or the muscles. This is achieved, for example, by using a liquid suspension of crystalline or non-ruthenium material having poor water solubility depending on the rate of dissolution, which is determined by the rate of t. In other embodiments, the::=knot:3 form*late and received' is achieved by dissolving or suspending the drug in an oil vehicle to achieve an injectable form of storage via biodegradable polymerization of the drug. Poly-internal vinegar sigma body poly... The microcapsule matrix in the father s 曰 is made. Depending on the ratio of drug to polymer and the nature of the particular polymer used, drug release 144〇87-sp-2〇〇9l 119-1 -90- 201019951 rate is controlled as appropriate. Examples of other biodegradable polymers are poly(orthoacids) and miscellaneous). The injectable formulation is also made, for example, by trapping the drug in a vesicle or microemulsion that is compatible with body tissues. The composition for rectal or vaginal administration is preferably a suppository, which is prepared by mixing the compound described herein with a suitable non-irritating excipient or carrier to produce, for example, cocoa butter, polyethyl b. A diol or suppository that is solid at ambient temperature but liquid at body temperature and therefore melts in the rectal or vaginal cavity and releases the active compound. Solid dosage forms for oral administration, including capsules, tablets, pills, powders and granules. In such a solid dosage form, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) filler or extender, for example Starch, lactose, sucrose, glucose, mannitol, and aspartic acid 'b) binders, such as stearyl cellulose, alginate, gelatin, polyethylene tetrahydrogen P, B, sucrose, and gum arabic, c) humectants, such as glycerol 'd) disintegrants, such as fat-filled, carbonated, potato or tapioca starch, alginic acid, certain citrates and sodium carbonate, e) dissolution blockers such as sarcophagus 〇 Absorbing accelerators, such as quaternary compounds, g) wetting agents, such as ethoxylated and glyceryl monostearate, h) absorbents, such as kaolin and bentonite 'and i) lubricants, such as talc, hard Calcium citrate, stearic acid lock, solid polyethylene glycol, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, this dosage form optionally contains a buffer. Solid compositions of a similar type are employed as fillers in soft and hard-filled gelatin capsules 144087-sp-20091119-l-91-201019951, using excipients such as lactose or milk sugar, and high molecular weight polyethylenes. Alcohol, etc. The solid dosage forms of tablets, dragees, capsules, pills and granules are formed, for example, with a coating and a shell layer such as an enteric coating and other described coatings. It may contain an opacifying agent as appropriate, and is also a composition which will only or preferentially release the active ingredient in a certain part of the intestinal tract, and examples of using the embedding composition in a delayed manner, as the case may be, include Polymeric substances and terpenoids. Solid compositions of a similar type are optionally employed as fillers in soft and hard-filled gelatin capsules, using excipients such as lactose or milk sugar, and high molecular weight polyethylene glycols and the like. The active compound is optionally in micro-coated form with or as a plurality of excipients as described above. The solid dosage forms of tablets, sugar readings, (d), pills and granules are optionally formed with a coating and a shell layer, such as an enteric coating, a release control coating and other described coatings. In such solid dosage forms, the living compound is mixed with, for example, at least one inert diluent such as cane sugar, lactose or starch. Such dosage forms include, as appropriate, inert diluents, other materials such as lubricants for pharmaceutical tablets and other pharmaceutical tablet auxiliaries such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, buffers are included as appropriate. It may contain an opacifying agent as the case may be, and is a composition which will only or preferentially occur in a certain part of the intestinal tract to produce an injury, as the case may be, in a delayed manner. Examples of the S-embedded composition include polymeric materials and butterflies. / The topical or transdermal dosage forms of the compounds described herein include ointment pastes! Cream, lotion, gel, powder, solution, (4) agent 1 144087-sp*20091119-l -92- 201019951 Music or stick music. The active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier and any required preservative or buffer. Ophthalmic formulas, ear drops, etc. are also intended to be covered. Ointments, pastes, creams and gels, in addition to the active compounds described herein, contain excipients, such as animal and vegetable fats, (iv) m-salt, starch, scutellaria, and cellulose. Derivatives, polyethylene-alcohol, polyoxin, bentonite, aristoloic acid, talc, and oxidized, or mixtures thereof. ,

The compositions described herein are formulated as liquid aerosols or inhalable dry powders as appropriate for delivery. The liquid aerosol formulation is primarily atomized into, for example, the size of the particles that are transported to the end of the trachea and the tracheal trachea, where the bacteria are left in patients with a branch tracheal infection, such as chronic bronchitis and pulmonary pathogens. In the entire airway, it descends to the branch trachea, twig gas & and lung host, especially; in the end and the respiratory tract tibial trachea. Bacteria can also be present in the lungs during the deterioration of the infection. The liquid aerosol and respirable dry powder formulation is preferably delivered throughout the branch trachea to the end twig trachea and finally to the host tissue. The aerosolized formulations described herein are transported using, for example, an aerosol forming device, such as a spray head, a vibrating perforated plate, or an ultrasonic nebulizer, preferably selected to allow formation of a mass intermediate average diameter of from about 5 to about 5 Aerosol particles between micrometers. Further, the formulation preferably has an equilibrium volume osmolality ionic strength and vapor concentration, and a minimum aerosolizable volume capable of delivering an effective amount of the compound described herein to the site of infection. Further, the aerosolized formulation preferably does not negatively impair the function of the airway 144087-sp-20091119-l 93·201019951 without causing undesirable side effects. An aerosolizing device suitable for use in the aerosol formulation administration described herein includes, for example, a spray head, a vibrating perforated plate, an ultrasonic atomizing tank, and a dry powder inhaler for supplying energy, which is capable of atomizing the formulation to be mainly in 1-5 Aerosol particle size in the micron size range. In the present application, it is meant primarily that at least 70%, but preferably greater than 90%, of all produced aerosol particles are in the range of μ5 microns. The spray atomization tank is acted upon by air pressure to break the liquid solution into aerosol droplets. The vibrating perforated plate atomization tank functions by utilizing the sonic vacuum generated by rapidly vibrating the perforated plate to squeeze the solvent droplets through the perforated plate. Ultrasonic nebulizers act by piezoelectric crystals that shear liquid into small aerosol droplets. A variety of suitable devices are available, including, for example, AeroNebTM and AeroDoseTM vibrating perforated plate atomization tanks (AeroGen, Sunnyvale, California), Sidestream® atomization tanks (Medic-Aid, West Sussex, England), Pari LC® and Pari LC Star® spray atomization tanks (Pari Respiratory Equipment, Inc., Richmond, Virginia) and AerosonicTM (DeVilbiss Medizinische Produkte (Deutschland) GmbH, Heiden, Germany) and UltraAire® (Omron Healthcare, Vernon Hills, Illinois) ultrasonic atomization tanks. The compounds described herein are formulated, for example, as a topical powder and spray for use in addition to the compounds described herein, including excipients such as lactose, talc, citric acid, aluminum hydroxide, hydrazine. Calcium acid and polyamide powder, or a mixture of such materials. Sprays may optionally contain conventional propellants, such as fluorocarbons. Transdermal patches have the added advantage of providing controlled delivery of the compound to the body. Such dosage forms are made, for example, by dissolving or dispensing the compound in a suitable medium 144087-sp-20091119-1 • 94· 201019951. Absorption enhancers are used to increase the flux of the compound across the skin, as appropriate. This rate is controlled, for example, by providing a rate controlling film or by dispersing the compound in a polymer matrix or gel. According to the methods of treatment described herein, bacterial sensation (d) is treated or prevented in a patient, such as a human or lower mammal, by administering a therapeutically effective amount of a compound described herein to the patient, In this amount and after, for example, the time necessary to achieve the desired result. By "therapeutically effective amount," as used herein, means a sufficient amount of a compound to treat a fine g infection at a reasonable benefit/risk ratio applicable to any medical treatment. However, it should be understood that The total daily usage of the compounds and compositions described herein will be determined by the responsible physician within the scope of safe and reliable medical judgment. The specific therapeutically effective dose for any particular patient will depend on a number of factors, including The severity of the condition and condition being treated; the specific compound used, the specific composition used; the age, weight, general health, sex and diet of the patient; the time of administration of the particular compound used, and the dosage Routes of drug and rate of excretion; duration of treatment; drugs that are combined or used with the particular compound employed; and similar in medical know-how: Factors: administered to humans or other mammals in single or divided doses The total daily dose of the compound described herein is, for example, 0. 01 to 50 mg / kg body weight ' or more usually 〇. 1 to 25 mg / kg body weight. A single dose composition will contain, for example, an approximate amount thereof to constitute the daily dose. In general, the therapeutic use described herein includes the administration of a single or multiple doses of about 1 mg to about 2 mg per day for a patient in need of such treatment. 144087-SP-20091119-1 -95- 201019951 The compounds described herein. Abbreviations In some embodiments, the abbreviations have been used in the following description of the drawings and examples, which are: AcOH is acetic acid; AIBN is azobisisobutyronitrile; nBu is n-butyl; Bu3 SnH is hydrogenated Butyltin; CDI is carbonyl diimidazole; DBU is 1,8-diazabicyclo[5. 4. 0] eleven-7-ene; DCC is dicyclohexylcarbodiimide; DCM is dichloromethane; DEAD is diethyl azodicarboxylate; DMF is dimethyl decylamine; DIEA or DIPEA is hydrazine , Ν-diisopropylethylamine; DMP is 2,2-dimethoxypropane; DMSO is dimethyl hydrazine (or fluorenyl hydrazine); DPPA is azide-phosphonium azide; Et3N is three Ethylamine; EtOAc is ethyl acetate; Et20 is diethyl ether; EtOH is ethanol; HOAc is acetic acid; HOSu is N-hydroxysuccinimide; LiHMDS or LiN(TMS)2 is lithium bis(trimethyldecyl)amine; MCPBA is m-p-perbenzoic acid; MeOH is methanol; MsCl is decanesulfonium chloride; NaHMDS or NaN(TMS)2 is sodium bis(trimethyldecyl)amine; NMO is N-methylmorpholine N-oxide; SOCl2 is sulfinium dichloride; PPTS is pyridinium p-toluenesulfonate; Pd(OAc)2 is palladium(II) acetate; PPh3 is triphenylphosphine; Py is pyridine; TFA is three Fluoroacetic acid; TEA is triethylamine; THF is tetrahydrofuran; TMSC1 is gasified trimethyl decane; TMSCF3 is tridecyl (trifluoromethyl)-decane; TPP is triphenylphosphine; TPAP is tetra-positive -propylammonium perrhenate; DMAP is 4-dimethylaminopyridine; Ts OH is p-toluenesulfonic acid; MsOH is methanesulfonic acid; OMs is methanesulfonate, OTs is toluenesulfonate; OTf is trifluoromethanesulfonate; Boc is tris-butoxycarbonyl; Fmoc is N - mercapto oxime oxycarbonyl; Su is amber quinone imine; Ph is phenyl; HBPyU is bismuth hexafluorophosphate-benzotriazol-1-yl-N,N,N',N'-bis(tetraindole) PyBOP is benzotriazole hexafluorophosphate-1- 144087-sp-20091119-1 •96- 201019951 oxylated tripyrrolidinyl scale; HATU is hexafluorophosphate N,N,N,,N, - Tetramethyl-indole-(7-nitrobenzotriazole small) uranium. Staphylococcus aureus resistant to dimethicillin Staphylococcus aureus (S.  Aureus) 'A spherical bacterium' is the most common cause of staphylococcal infection. Staphylococcus aureus is known to cause a range of diseases 'from small skin infections, such as acupuncture, blistering, blistering, bee stings, folliculitis, sputum, sputum, scaly skin syndrome, abscesses, To the _ threat to life diseases, such as pneumonia, meningitis, osteomyelitis endocarditis, toxic shock syndrome and septicemia. Furthermore, Staphylococcus aureus is one of the most common causes of infection in hospitals, often resulting in wound infection after surgery. Monomethoxyphthalicillin was introduced in the late 1950s to treat infections caused by Staphylococcus aureus resistant to penicillin. It has previously been reported that S. aureus isolates are resistant to dimethicillin (resistance to dimethomycin-resistant S. aureus MRSA). The methicillin resistance gene (mecA) encodes a ureomycin-binding protein that is resistant to p-methicillin which is susceptible to infection. The mecA line is carried on the mobile gene building: (Staphylococcal chromosome mec (SCCsccm)), four of which have been described: the description is different in size and genetic composition. The penicillin-binding protein line, which is resistant to p-methicillin, allows resistance to endogenous antibiotics' and excludes its clinical use during MRSA infection. In one aspect, a method of treating a patient having a drug-resistant bacterium, comprising administering to the patient a compound of formula 1, or a pharmaceutically acceptable salt, a brew, a solvate thereof, an alkylated quaternary ammonium salt, Stereoisomer, tautomer 144087-sp-20〇91119-1 -97- 201019951 substance or prodrug. In a specific embodiment, the bacterium is a Gram-positive bacterium. In another embodiment, the 'I blue positive bacteria is Staphylococcus aureus. In the specific embodiment of the invention, the 'S. aureus strain is resistant to the indoleamine antibiotic or is ruminant. In still further embodiments, the in-line guanamine antibiotic is attributed to the class of penicillin. In a further specific embodiment, the indoleamine antibiotic is dimethoxyphenylpenicillin. In another embodiment, the patient has Staphylococcus aureus resistant to dimethoxyphthalicillin. In a specific embodiment, the indole steroid antibiotic is fluoropenicillin. In another embodiment, a method of treating a patient having a resistance to a bis-penicillin-resistant bacterium comprising administering to the patient a compound of formula (I) or a pharmaceutically acceptable salt or ester thereof , a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is ruthenium against penicillin. Also disclosed herein is a method of treating a patient having a resistance to dioxetinomycin, comprising administering a compound of Formula 1, or a pharmaceutically acceptable salt, ester, solvate, or alkane thereof; A quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient has been tested for a bacterium resistant to dimethicillin. In one embodiment, the patient is screened for a bis- phenoxymycin resistant bacterium. In another embodiment, the patient screening is performed via a nasal culture. In a specific embodiment, the bacteria resistant to dimethoxyphthalicillin are detected by wiping the nostrils of the patient and separating the bacteria. In another embodiment, real-time PCR and/or quantitative PCR is used to determine if a patient has a resistance to dimethicillin. 144087-SP-20091119-1 -98-201019951 In one embodiment is a method of treating a patient having a first-generation cephalosporin-resistant bacterium comprising administering a compound of formula 1 or a pharmaceutical thereof An acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the patient is first to: cephalosporin g In a specific embodiment, the bacterial line is resistant to the first-generation cephalosporin. In a further embodiment, the bacterial line is resistant to cephalosporin νπ. In another embodiment, the bacterial line is resistant to ❿mamine tauspulin®. In yet another embodiment, the bacterial strain is resistant to cephalosporin. In one embodiment, the bacteria are resistant to cephalosporin III. In another specific embodiment, the bacteria are resistant to ceftranin. In another specific embodiment, the bacterial line is resistant to cefaloridine. In yet another embodiment, the bacterial line is resistant to ceflotin. In a further specific embodiment, the bacterial line is resistant to cefepime. In yet another specific embodiment, the bacterial line is held on the head and the well is resistant. In one implementation: ❹, the bacteria are resistant to cefazoflur (cefazaflur). In another specific embodiment, the bacterial line is resistant to cefazed〇ne. In yet another embodiment, the bacterium system has a drug resistant head. In a further embodiment, the bacterial line is resistant to cefadine. In a further embodiment, the bacteria are resistant to cefroxaxadine (cefr〇xadine). In a specific embodiment, the bacteria are resistant to sifirazole _e_. In a specific embodiment, a method of treating a patient having a second-generation cephalosporin-resistant bacterium comprising administering a compound of formula (1) or 144087-SP-20091119-1 • 99 - 201019951 pharmaceutically acceptable salts, hydrazines, solvates, alkylated tetrabasic salts, stereoisomers, tautomers or prodrugs thereof, wherein the patient is a second-generation cephalosporin Anti-throwing. In another embodiment, the bacteria are resistant to the second generation cephalosporins. In a further embodiment, the bacteria are resistant to gas cephalosporins. In another embodiment, the bacteria are resistant to Westwind Nissan (4) onieid. In yet another embodiment (4), the bacteria are resistant to cefpr〇zil. In one embodiment, the bacteria are resistant to cephalexin. In another embodiment, the bacterial line is resistant to sylvestre (ceftlz〇nam). In another specific embodiment, the bacterial line is resistant to siflumeta. In yet another embodiment, the bacterium is resistant to severiftan (cef〇te_! In a further embodiment, the bacterium is resistant to cephalosporin p-cetin. In one embodiment, a method of treating a patient having a third-generation cephalosporin-resistant bacterium comprising administering a compound of Formula 1, or a pharmaceutically acceptable salt, ester, solvate thereof, alkylation thereof a quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is ruminant to a third-generation cephalosporin. In another specific embodiment, the bacterium is a third-generation cephalosporin The bacteriocin is resistant. In further embodiments, the bacterium is resistant to cefcapene. In another specific embodiment, the bacterium is resistant to cefdaloxime. In another embodiment, the bacterium is resistant to cefdinir. In one embodiment, the bacterium is resistant to cefdit ren. In the examples, the 'bacterial line is resistant to cefixime in West Africa. Drug 144087-sp-20091119-l -100- 201019951 Sex. In another specific embodiment, the bacterium is resistant to cefinenoxime. In yet another embodiment, the bacterium is west The cefodizime is resistant. In further embodiments, the bacterium is resistant to cefotaxime. In still further embodiments, the bacterium is placed on a cefpimizole Drug resistance. In one embodiment, the bacterial line is resistant to cefpodoxime. In another specific embodiment, the bacterial line is resistant to cefteram. In another embodiment, the bacterial line is resistant to ceftibuten. In further embodiments, the bacterial line is resistant to ceftiofiir. In still further embodiments, The bacterial line is resistant to ceftiolene. In one embodiment, the bacterial line is resistant to cefizoxime. In another specific embodiment, the bacterium is against ceftriaxone ( Ceftriax One) is resistant. In yet another embodiment, the bacterium is resistant to cefoperazone. In still further embodiments, the bacterium is resistant to ceftazidime. In one embodiment, a method of treating a patient having a fourth-generation cephalosporin-resistant bacterium comprising administering a compound of formula 1 or a pharmaceutically acceptable salt, ester or solvate thereof An alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is ruminant to the fourth generation cephalosporin. In another specific embodiment, the bacteria are resistant to the fourth generation cephalosporins. In a further embodiment, the bacteria are resistant to cefclidin. In another specific embodiment, the bacterial line is resistant to cefepime. In yet another embodiment, the bacterial line is resistant to cefluprenam. In one embodiment of 144087-SP-20091119-1 -101 - 201019951, the bacterial line is resistant to cefoselis. In another embodiment, the bacterial line is resistant to cefozopran. In another specific embodiment, the bacteria are resistant to cefpirome. In yet another specific embodiment, the bacterial line is anti-throwing to cefquinome. In one embodiment, a method of treating a patient having a drug resistant to carbapenem, comprising administering a compound of formula (I) or a pharmaceutically acceptable salt, ester or solvent thereof a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is anti-throwing to carbapenem. In another embodiment, the bacterial line is resistant to carbapenem. In a further embodiment, a method of treating a patient having a imipenem-resistant bacterium comprising administering a compound of formula (I) or a pharmaceutically acceptable salt thereof, vinegar, or a solvent a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to imipenem. In another embodiment, a method of treating a patient having a drug resistant to menotem, comprising administering a compound of formula (I) or a pharmaceutically acceptable salt or ester thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to metopem. In yet another embodiment, a method of treating a patient having a tytapenem-resistant bacterium comprising administering a compound of formula (I) or a pharmaceutically acceptable salt or ester thereof , solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, of which 144087-SP-20091119-1 •102· 201019951 Bacterial line is resistant to ertapenem Medicinal. In one embodiment, a method of treating a patient having a resistance to faropenem-resistant bacteria comprising administering a compound of formula (I) or a pharmaceutically acceptable salt, ester or solvent thereof a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to faropenem (faropenem). In another embodiment, a method of treating a patient having a drug resistant to doricanem comprising administering a compound of formula (I) or a pharmaceutically acceptable salt, ester or solvent thereof a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to dorisenem. In another embodiment, a method of treating a patient having a resistance to a panicenem bacterium comprising administering a compound of formula (I) or a pharmaceutically acceptable salt thereof, a solvate, a quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to panipenem. In yet another embodiment, a method of treating a patient having a biapenem-resistant bacterium comprising administering a compound of formula (I) or a pharmaceutically acceptable salt or ester thereof a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to biapenem. In one aspect, a method of treating a patient having a drug-resistant bacterium, comprising administering to the patient a compound of formula (II) or a pharmaceutically acceptable salt, ester, solvate thereof, alkylated quaternary ammonium salt thereof a salt, stereoisomer, tautomer or prodrug. In a specific embodiment, the bacterium is Gram-positive 144087-SP-20091119-1 -103 - 201019951 bacterium. In another specific embodiment, the Gram-positive bacterium is Staphylococcus aureus. In a further embodiment, the S. aureus strain is resistant or ruminant to endogenous antibiotics. In yet a further embodiment, the endogenous antibiotic antibiotic is attributed to the class of penicillin. In a further embodiment, the indoleamine antibiotic is dimethoxy acesulfame. In yet another embodiment, the patient has Staphylococcus aureus resistant to dimethoxyphthalocyanine. In one embodiment, the finely available amine antibiotic is air gas penicillin. In another embodiment, a method of treating a patient having a resistance to bis-penicillin-resistant bacteria, comprising administering to the patient a compound of formula (II), or a pharmaceutically acceptable salt, ester thereof, a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is ruthenium against diclofenac. Also disclosed herein is a method of treating a patient having a methicillin-resistant bacterium comprising administering a compound of formula (11) or a pharmaceutically acceptable salt, ester or solvate thereof An alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient has been tested for a bacterium having resistance to dimethicillin. In one embodiment, the patient is screened for methicillin resistant bacteria. In another embodiment, the patient is selected from the nasal culture. In the specific embodiment, the methicillin-resistant bacteria were wiped out of the patient's nostrils by 2, and were isolated from the bacteria. In another embodiment, real-time PCR and/or quantitative PCR are employed to determine if a patient has a resistance to methicillin. In one embodiment, a method of treating a patient having a first-generation cephalosporin 144087-SP-20091119-1 -104-201019951 dying resistant bacteria comprising administering a compound of formula (9) or a pharmaceutically thereof thereof The salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug may be attached, wherein the patient is ruminant to the first generation cephalosporin. In one embodiment, the bacterial line is resistant to the first lencosporin. In the specific embodiment, the bacteria are resistant to the scorpion® VII. In another embodiment, the bacteria are resistant to the amine cephalosporin. In yet another embodiment, the fine beta (tetra) is resistant to cephalosporins. In a specific implementation, the bacteria are resistant to cephalosporin. In another specific embodiment, the bacteria are resistant to ceftranin. In another specific embodiment, the bacterial line is resistant to cefaloridine. In yet another embodiment, the bacterial line is resistant to cefolodin iT (cefalotin). In a further specific example, the bacterial line was resistant to cephalosporin p than sulfur. In yet another specific embodiment, the bacterial line is resistant to head and head. In one embodiment, the bacteria are resistant to cefazoflu. In another specific example, the bacterium is resistant to _ _ _ buckle -). In yet another embodiment, the bacteria are resistant to the head. Yu Jinyi: In the specific example, the 'bacterial line is resistant to cefadine. In a further example, the bacterium was resistant to cefr〇xadine. In the specific embodiment, the 'bacterial line' is resistant to cough. In one embodiment, a method of treating a patient having a second-generation cephalosporin-resistant bacterium comprising administering a compound of the formula or a pharmaceutically acceptable salt thereof, , solvate, alkylate quaternary salt, 144087-sp-2009l 119-1 -105- 201019951 stereoisomers, tautomers or prodrugs, wherein the patient is a second-generation cephalosporin For rumors. In another specific embodiment, the bacteria are resistant to the second generation cephalosporins. In a further embodiment, the bacteria are resistant to gas cephalosporins. In another specific embodiment, the bacteria are resistant to cefonicid. In yet another embodiment, the bacterial line is resistant to cefprozil. In one embodiment, the bacteria are resistant to cephalosporin. In another specific embodiment, the bacterial line is resistant to cefuzonam. In another specific embodiment, the bacterial line is resistant to cefmetazole. In yet another embodiment, the bacterial line is resistant to cefotetan. In a further embodiment, the bacterial line is resistant to cefosime. In one embodiment, a method of treating a patient having a third-generation cephalosporin-resistant bacterium comprising administering a compound of formula (II) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the patient is ruminant to the third generation cephalosporin. In another specific embodiment, the bacteria are resistant to third generation cephalosporins. In a further embodiment, the bacteria are resistant to cefcapene. In another specific embodiment, the bacterial line is resistant to cefdaloxime. In yet another specific embodiment, the bacterial line is resistant to cefdinir. In a specific embodiment, the bacterial line is resistant to cefditoren. In another specific embodiment, the bacterial line is resistant to cefixime. In another specific embodiment, the bacterial line is resistant to cefmenoxime 144087-sp-20091119-l-106-201019951. In yet another embodiment, the bacterial line is resistant to cefodizime. In a further embodiment, the bacterial line is resistant to cefotaxime. In yet a further embodiment, the bacterial line is resistant to cefpimizole. In one embodiment, the bacterial line is resistant to cefpodoxime. In another specific embodiment, the bacterial line is resistant to cefteram. In yet another embodiment, the bacterial line is resistant to cettibuten (ceftibuten). In a further embodiment, the bacterial line is resistant to ceftiofur. In yet a further embodiment, the bacterial line is resistant to ceftiolene. In one embodiment, the bacterium is resistant to ceftizoxime. In another specific embodiment, the bacteria are resistant to ceftriaxone. In yet another embodiment, the bacterium is resistant to cefoperazone. In still further embodiments, the bacterium is resistant to ceftazidime. In one embodiment, a method of treating a patient having a fourth-generation cephalosporin-resistant bacterium comprising administering a compound of formula (II) or a pharmaceutically acceptable salt, ester or solvent thereof a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient line is ruminant to the fourth generation cephalosporin. In another specific embodiment, the bacteria are resistant to the fourth generation cephalosporins. In a further embodiment, the bacteria are resistant to cefclidin. In another specific embodiment, the bacterial line is resistant to cefepime. In yet another embodiment, the bacterial line is resistant to cefluprenam. In a specific embodiment, the bacteria are resistant to cefoselis. In another embodiment, the bacterium is resistant to cefozopran. In another specific embodiment, the bacteria are resistant to cefpirome. In yet another embodiment, the bacterium is cefquinome, and in one embodiment is a patient having a resistance to carbapenem resistant bacteria. a method comprising administering a compound of formula (II) or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein the disease The affected line is ruminant against carbapenem. In another embodiment, the bacterial line is resistant to several carbapenems. In a further embodiment, a method of treating a patient having a imipenem-resistant bacterium comprising administering a compound of formula (II) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the bacterial line is resistant to imipenem. In another embodiment, a method of treating a patient having a drug resistant to menotem, comprising administering a compound of formula (或其) or a pharmaceutically acceptable salt or ester thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to metopem. In yet another embodiment, a method of treating a patient having a drug resistant to ertapenem, comprising administering a compound of formula (Π) or a pharmaceutically acceptable salt thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to ertapenem. In a specific embodiment 144087-SP-2009U19-1 -108-201019951, a method for treating a patient having a resistance to faropenem-resistant bacteria, comprising administering a compound of the formula (Π) or A pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein the bacterial line is resistant to faropenem. In another embodiment, a method of treating a patient having a drug resistant to doricanem comprising administering a compound of formula (II) or a pharmaceutically acceptable salt, ester or solvent thereof a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to dorisenem. In another embodiment, a method of treating a patient having a resistance to a panicenem bacterium comprising administering a compound of formula (II), or a pharmaceutically acceptable salt thereof, vinegar, a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to panipenem. In yet another embodiment, a method of treating a patient having a biapenem-resistant bacterium comprising administering a compound of formula (II) or a pharmaceutically acceptable salt or ester thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to biapenem. In one aspect, a method of treating a patient having drug-resistant bacteria, comprising administering to the patient a compound of formula (III) or a pharmaceutically acceptable salt, ester, solvate thereof, alkylated quaternary ammonium a salt, stereoisomer, tautomer or prodrug. In a specific embodiment, the bacterium is a Gram-positive bacterium. In another specific embodiment, the Gram-positive bacterium is Rhubarb 144087-sp-20091119-l-109-201019951. In further embodiments, the S. aureus strain is resistant to or resistant to /3-indoleamine antibiotics. In yet a further embodiment, the 'alkylmidine antibiotic is attributed to the class of penicillin. In a further specific embodiment, the endogenous antibiotic is methicillin. In yet another embodiment, the patient has Staphylococcus aureus resistant to dimethicillin. In one embodiment, the indoleamine antibiotic is fluoropenicillin. In another embodiment, a method of treating a patient having a resistance to bis-penicillin, including the disease Administering a compound of formula (m) or a pharmaceutically acceptable salt thereof, an ester, a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is Biqi penicillin is ruminant. Also disclosed herein is a method of treating a patient having a resistance to dimethoxyphenylpenicillin comprising administering a compound of formula (m) or a pharmaceutically acceptable salt, ester or solvent thereof. An alkylated quaternary ammonium salt, an isomer or a prodrug, wherein the patient has been determined to have a resistance to = oxygen: the penicillin-resistant bacteria. In one embodiment, the diseased line is directed against a bis- phenoxymycin resistant bacterium. In another example: In the examples, the patient screening is performed via a nasal culture. In the specific embodiment, the methicillin 1 household, and the monthly (four) sexual bacteria are detected by wiping the nostrils of the patient and being isolated from the bacteria. In the case of 'using real-time PCR and/or quantitative PCR, ^ M ' is whether the patient has a drug resistant to dimethoxyphthalicillin. In one embodiment, the method is a method for treating and/or having a contraceptive bacterium that is resistant to the first generation of cephalosporin, or a compound of formula (III) or 144087-sp- 20091119-1 -110.  201019951

a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein the patient is resistant to the first generation cephalosporin . In one embodiment, the bacterial line is resistant to the first generation cephalosporins. In a further embodiment the 'bacterial line is resistant to cephalosporin VII. In another embodiment, the bacterium is resistant to hydroxyaminophen cephalosporin. In yet another embodiment, the bacterial strain is resistant to cephalosporin beta in a particular embodiment wherein the bacterial strain is resistant to cephalosporin III. In another specific embodiment, the bacteria are resistant to ceftranin. In another specific embodiment, the bacterial line is resistant to cefaloridine. In yet another embodiment, the bacterial line is resistant to cefodylin. In a further specific embodiment, the bacterial line is resistant to cefepime. In yet another specific embodiment, the bacterial line is resistant to cephalosporin. In one embodiment, the bacterial line is resistant to cefazo aurethane (cefazaAur). In another specific embodiment, the bacterial line is resistant to cefazedone. In yet another embodiment, the bacterial line is resistant to cefazolin. In a further embodiment, the bacteria system is resistant to cefadine. Further, in a specific example t, the bacteria system is resistant to sifosadine (tetra). In one embodiment, the bacterium is resistant to sevoflurazole. In one embodiment, a method of treating a patient having a second-generation cephalosporin: drug-resistant bacterium, comprising administering a compound of the formula or a salt thereof, a solvent a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is ruminant against the second 144087-SP-20091119-1, 111·201019951 cephalosporin . In another specific embodiment, the bacteria are resistant to the second generation cephalosporins. In a further embodiment, the bacteria are resistant to gas cephalosporins. In another specific embodiment, the bacteria are resistant to cefonicid. In yet another embodiment, the bacterial line is resistant to cefprozil. In one embodiment, the bacteria are resistant to cephalosporin. In another specific embodiment, the bacterial line is resistant to cefuzonam. In another specific embodiment, the bacterial line is resistant to cefmetazole. In yet another embodiment, the bacterial line is resistant to cefotetan. In a further embodiment, the bacterial line is resistant to cefosime. In one embodiment, a method of treating a patient having a third-generation cephalosporin-resistant bacterium comprising administering a compound of formula (III) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the patient is ruminant to the third generation cephalosporin. In another specific embodiment, the bacteria are resistant to third generation cephalosporins. In a further embodiment, the bacteria are resistant to cefcapene. In another specific embodiment, the bacterial line is resistant to cefdaloxime. In yet another specific embodiment, the bacterial line is resistant to cefdinir. In a specific embodiment, the bacterial line is resistant to cefditoren. In another specific embodiment, the bacterial line is resistant to cefixime. In another specific embodiment, the bacterial line is resistant to cefmenoxime. In yet another embodiment, the bacterial line is resistant to Sifudi well 144087-SP-20091119-1 201019951 (cefodizime). In a further embodiment, the bacterial line is resistant to cefotaxime. In yet a further embodiment, the bacterium is against sifami. Sitting (cefpimizole) is resistant. In one embodiment, the bacterial line is resistant to cefpodoxime. In another specific embodiment, the bacterial line is resistant to cefteram. In yet another embodiment, the bacterial line is resistant to cettibuten (ceftibuten). In a further embodiment, the bacterial line is resistant to ceftiofur. In yet a further embodiment, the bacterial line is resistant to ceftiolene. In one embodiment, the bacterium is resistant to ceftizoxime. In another embodiment, the bacteria are resistant to ceftriaxone. In yet another embodiment, the bacterial line is resistant to cefoperazone. In still further embodiments, the bacterial line is resistant to ceftazidime. In one embodiment, a method of treating a patient having a fourth-generation cephalosporin-resistant bacterium comprising administering a compound of formula (ΠΙ) or a pharmaceutically acceptable salt, ester, or solvent thereof a compound, an alkylated quaternary salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is ruminant to the fourth generation cephalosporin. In another specific embodiment, the bacteria are resistant to the fourth generation cephalosporins. In a further embodiment, the bacterium is resistant to cefclidin. In another embodiment, the bacterium is resistant to cefepime. In yet another embodiment, the bacterial line is resistant to cefluprenam. In a specific embodiment, the bacteria are resistant to cefoselis. In another embodiment, the bacterium is resistant to cefozopran 144087-SP-20091119-1 -113-201019951. In another specific embodiment, the bacteria are resistant to cefpirome. In yet another embodiment, the bacterium is cefquinome ectopic. In one embodiment, the patient is afflicted with a carbapenem-resistant bacterium. a method comprising administering a compound of formula (III) or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein the disease The affected line is anti-throwing to carbapenem. In another embodiment, the bacterial line is resistant to carbapenem. In a further embodiment, a method of treating a patient having a imipenem-resistant bacterium comprising administering a compound of formula (III) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the bacterial line is resistant to imipenem. In another embodiment, a method of treating a patient having a drug resistant to menotem, comprising administering a compound of formula (III) or a pharmaceutically acceptable salt or ester thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to metopem. In yet another embodiment, a method of treating a patient having a drug resistant to ertapenem, comprising administering a compound of formula (III) or a pharmaceutically acceptable salt or ester thereof , a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to ertapenem. In one embodiment is a method of treating a patient having resistance to faropenem (faropenem) 144087-sp-20091119-l • 114-201019951 comprising administering a compound of formula (III) or A pharmaceutically acceptable salt, vinegar, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein the bacterial line is resistant to faropenem. In another embodiment, a method of treating a patient having a drug resistant to doricanem comprising administering a compound of formula (III) or a pharmaceutically acceptable salt, ester or solvent thereof a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to dorisenem. In another embodiment, a method of treating a patient having a resistance to a panicenem bacterium comprising administering a compound of formula (III), or a pharmaceutically acceptable salt thereof, vinegar, a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to panipenem. In yet another embodiment, a method of treating a patient having a biapenem-resistant bacterium comprising administering a compound of formula (III) or a pharmaceutically acceptable salt or ester thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to biapenem. In one aspect, a method of treating a patient having a drug-resistant bacterium, comprising administering to the patient a compound of formula (IV) or a pharmaceutically acceptable salt, ester, solvate thereof, alkylated quaternary ammonium a salt, stereoisomer, tautomer or prodrug. In a specific embodiment, the bacterium is a Gram-positive bacterium. In another specific embodiment, the Gram-positive bacterium is Staphylococcus aureus. In a further embodiment, the S. aureus strain is 144087-SP-20091119-1 • 115 - 201019951. The indoleamine antibiotic is resistant or ruminant. In yet a further embodiment, the indoleamine antibiotic is assigned to the class of penicillin. In the embodiment of the invention, the indoleamine antibiotic is dimethoxyphenylpenicillin. In yet another embodiment, the patient has Staphylococcus aureus resistant to dimethicillin. In a specific embodiment, each of the indoleamine antibiotics is fluoropenicillin. In another embodiment, a method of treating a patient having a resistance to bis-penicillin-resistant bacteria, comprising administering to the patient a compound of formula (IV) or a pharmaceutically acceptable salt or ester thereof , a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient is ruthenium against diclofenac. Also disclosed herein is a method of treating a patient having a methicillin-resistant bacterium comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt, ester or solvate thereof. An alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the patient has been tested for a bacterium having resistance to dimethicillin. In one embodiment, the patient is screened for a bis- phenoxymycin resistant bacterium. In another specific embodiment, the patient screening is performed via a nasal culture. In the first step, the bacteria resistant to dimethicillin were detected by wiping the nostrils of the patient and isolated from the bacteria. In another embodiment, an instant PCR and/or a PCR is used to determine whether the patient has a resistance to methicillin. π A specific example of a method for treating a first-generation venom-resistant bacteria, comprising administering a pharmaceutically acceptable salt, a solvate. The fourth grade of the alkylation is 144087^sp-20091119-1 * 116- 201019951

Stereoisomers, tautomers or prodrugs in which the patient is ruminant against the first generation cephalosporin. In one embodiment, the bacterial line is resistant to the first generation cephalosporins. In a further embodiment, the bacterial line is resistant to cephalosporin VII. In another specific embodiment, the bacterial line is resistant to the amine cephalosporin. In yet another embodiment, the bacterial strain is resistant to cephalexin. In one embodiment, the bacteria are resistant to cephalosporin m. In another specific embodiment, the bacteria are resistant to ceftranin. In another specific embodiment, the bacterial line is resistant to cefaloridine. In yet another embodiment, the bacterial line is resistant to ceflotin. In a further specific embodiment, the bacterial line is resistant to cefepime. In yet another specific embodiment, the bacterial line is resistant to cephalosporin. In one embodiment, the bacterial line is resistant to cefazaflur. In another specific embodiment, the bacterial line is resistant to cefazedone. In yet another embodiment, the bacterial line is resistant to head and spit. In a further embodiment, the bacterial line is resistant to cefadine. In the further example, in the embodiment, the bacteria system is resistant to cefroxadine; in the embodiment, the bacteria system is to Sifti. Sitting (ceftezole) is resistant. A method for treating a patient having a forgotten stroke of a second-generation cephalosporin-resistant bacterium, comprising administering a compound of the formula (IV) or a pharmaceutically thereof thereof; Acceptable sleep, | S day, solvate, alkylated quaternary ammonium salt, stereoisomer, mutual mutation from Qiyi... Qiuwuwu or prodrug, in which the patient is second The cephalosporin is a retrospective. In a further embodiment, the bacterium is resistant to the second generation cephalosporin of 144087-sp-20091119-1 '117-201019951. In a further embodiment, the bacteria are resistant to gas cephalosporins. In another specific embodiment, the bacteria are resistant to cefonicid. In yet another embodiment, the bacterial line is resistant to cefprozil. In one embodiment, the bacteria are resistant to cephalosporin. In another specific embodiment, the bacterial line is resistant to cefuzonam. In another specific embodiment, the bacteria are resistant to cefmetazole. In yet another embodiment, the bacterial line is resistant to cefotetan. In a further embodiment, the bacterial line is resistant to cefosime. In one embodiment, a method of treating a patient having a third-generation cephalosporin-resistant bacterium comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the patient is ruminant to the third generation cephalosporin. In another specific embodiment, the bacteria are resistant to third generation cephalosporins. In a further embodiment, the bacteria are resistant to cefcapene. In another specific embodiment, the bacterial line is resistant to cefdaloxime. In yet another specific embodiment, the bacterial line is resistant to cefdinir. In a specific embodiment, the bacterial line is resistant to cefditoren. In another specific embodiment, the bacterial line is resistant to cefixime. In another specific embodiment, the bacterial line is resistant to cefmenoxime. In yet another embodiment, the bacterial line is resistant to cefodizime. In a further embodiment, the bacterial line is resistant to head 144087-SP-20091119-1 -118-201019951 cefotaxime. In yet a further embodiment, the bacterial line is resistant to cefpimizole. In one embodiment, the bacterial line is resistant to cefpodoxime. In another specific embodiment, the bacterial line is resistant to cefteram. Further: In another specific embodiment, the bacterial line is resistant to cettibuten (ceftibuten). In a further embodiment, the bacterial line is resistant to ceftiofiir. In yet a further embodiment, the bacterial line is resistant to ceftiolene. In one embodiment, the bacterial line is resistant to ceftizoxime. In another specific embodiment, the bacteria are resistant to ceftriaxone. In yet another embodiment, the bacterial line is resistant to cefoperazone. In still further embodiments, the bacterial line is resistant to ceftazidime. In one embodiment, a method of treating a patient having a fourth-generation cephalosporin-resistant bacterium comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, φ stereoisomer, tautomer or prodrug, wherein the patient is ruminant to the fourth generation cephalosporin. In another specific embodiment, the bacteria are resistant to the fourth generation cephalosporins. In a further embodiment, the bacteria are resistant to cefclidin. In another specific embodiment, the bacterial line is resistant to cefepime. In yet another embodiment, the bacterial line is resistant to cefluprenam. In a specific embodiment, the bacteria are resistant to cefoselis. In another embodiment, the bacterial line is resistant to cefozopran. In another specific embodiment, the bacterial line is resistant to cefpirome 144087-sp-20091119-l-119-201019951. In yet another embodiment, the 'bacterial line is cefquinome, which is a ruminant. In one embodiment, a patient having a resistance to carbapenem resistant bacteria is used. a method comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt thereof, stereoisomer, tautomer or prodrug thereof The affected line is anti-throwing to carbaeneem. In another embodiment, the bacterial line is resistant to carbapenem. In a further embodiment, a method of treating a patient having a imipenem-resistant bacterium comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the bacterial line is resistant to imipenem. In another embodiment, a method of treating a patient having a drug resistant to Meropenem, comprising administering a compound of Formula (IV) or a pharmaceutically acceptable salt or ester thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to metopem. In yet another embodiment, a method of treating a patient having a tytapenem-resistant bacterium comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt or ester thereof a solvate 'alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the bacterial line is resistant to ertapenem. In one embodiment, a method of treating a patient having a resistance to faropenem (faropenem) comprising administering a compound of formula (IV) or a pharmaceutically acceptable 144087-SP-20091119-1 -120· 201019951 Accepted salts, esters, solvates, alkylated quaternary ammonium salts, stereoisomers, tautomers or prodrugs wherein the bacterial line is resistant to faropenem (faropenem). In another embodiment, a method of treating a patient having a drug resistant to doricanem comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt, ester or solvent thereof a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to dorisenem. In another embodiment, a method of treating a patient having a resistance to a panicenem bacterium comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt thereof, a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to panipenem. In yet another embodiment, a method of treating a patient having a biapenem-resistant bacterium comprising administering a compound of formula (IV) or a pharmaceutically acceptable salt thereof, vinegar a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to biapenem. In one aspect, a method of treating a patient having a drug-resistant bacterium, comprising administering to the patient a compound of formula (V) or a pharmaceutically acceptable salt, ester, solvate thereof, alkylated quaternary ammonium a salt, stereoisomer, tautomer or prodrug. In a specific embodiment, the bacterium is a Gram-positive bacterium. In another specific embodiment, the Gram-positive bacterium is Staphylococcus aureus. In further embodiments, the S. aureus strain is resistant to or resistant to /3-indoleamine antibiotics. Further specific examples 144087-SP-20091119-1 -121 - 201019951 The endophthalic antibiotics belong to the class of penicillin. In a further specific embodiment, the indoleamine antibiotic is dimethyl phthalicillin. In yet another embodiment, the patient has Staphylococcus aureus resistant to dimethoxyphthalicillin. In a specific embodiment, the indole steroid antibiotic is fluoropenicillin. In another embodiment, a method of treating a patient having a resistance to bis-penicillin-resistant bacteria, comprising administering to the patient a compound of formula (V) or a pharmaceutically acceptable salt or ester thereof , a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a rigid drug, wherein the patient is anti-throwing to the penicillin. Also disclosed herein is a method of treating a bacterial disease having resistance to dimethicillin comprising administering a compound of formula (V) or a pharmaceutically acceptable salt, ester or solvate thereof. An alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug wherein the patient has been tested to have resistance to dimethicillin. In the specific embodiment, the patient roll

The selection of dimethoxy phenyl penicillin-resistant bacteria. In the other item and in the H embodiment, the patient (4) is subjected to a nasal culture. In the examples, the methicillin-resistant bacteria were detected by uncovering the nostrils of the patient and isolated from the bacteria. In another implementation, you can make an immediate (10) and / or ^ amount of PCR to determine whether the patient has purple methicillin-resistant bacteria.句一禋//Oral therapy has a method for a first-generation head: a patient suffering from a drug-resistant bacterium, which comprises administering a compound of the formula (7) to a pharmaceutically acceptable salt 1, a solvate thereof, an alkylation group Ammonium stereoisomers, tautomers or prodrugs, in which the patient is paired: 144087-sp-20091119-1 -122- 201019951 The cephalosporin is counter-persecution. In one embodiment, the bacterial line is resistant to the first generation cephalosporins. In a further embodiment, the bacterial line is resistant to cephalosporin VII. In another specific embodiment, the bacterial line is resistant to the amine cephalosporin. In yet another embodiment, the sequence is: the strain is resistant to cephalosporin. In one embodiment, the bacterium is resistant to cephalosporin III. In another specific embodiment, the bacteria are resistant to ceftranin. In another specific embodiment, the bacterial line is resistant to cefaloridine. In yet another embodiment, the bacterial line is resistant to cefalindin. In a further specific embodiment, the bacterial line is resistant to cefodizime. In yet a further embodiment, the bacterial line is resistant to cefatridin. In one embodiment, the bacteria are resistant to cefazoflu. In another specific κ regimen, the bacterial line is resistant to cefazedone. In yet another embodiment, the bacterial line is resistant to cefazolin. In a further embodiment, the bacterial line is resistant to cefadine. In a further embodiment, the 'bacterial line' is resistant to sefloxine (cefro domain ne) ('b. In the specific embodiment, the bacterium is against eeftezde). Drug resistance. In a specific embodiment, a method of treating a patient having a second-generation cephalosporin-reducing bacterium, comprising administering a compound or a pharmaceutically acceptable salt thereof, 酉Or a solvate, an alkylated quaternary salt, an isomer 1 isomer or a prodrug, wherein the patient is counter-intuitive for the second-generation cephalosporin. In the case of the bacterial system (4), the second-generation cephalosporin is resistant. In a further specific embodiment, the bacterial line 144087-SP-20091119-1 * 123-201019951 is resistant to chlorocephalosporin. In another specific embodiment In the other embodiment, the bacterial line is resistant to cefonicid. In yet another embodiment, the bacterial line is resistant to cefprozil. In one embodiment, the bacterial line is Resistant to cephalosporin. In another specific embodiment, the bacterium is placed on the south of the cefozona (cefuzona) m) is resistant. In another specific embodiment, the bacterial line is resistant to cefmetazole. In yet another embodiment, the bacterial line to cefotetan (cefotetan) Resistant to pharmaceuticals. In a further embodiment, the bacterium is resistant to cefaquinone. In one embodiment, a method of treating a patient having a third-generation cephalosporin-resistant bacterium Which comprises administering a compound of the formula (V) or a pharmaceutically acceptable salt thereof, a S, a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the disease The affected line is ruminant to the third generation cephalosporin. In another specific embodiment, the bacterial line is resistant to third generation cephalosporins. In further embodiments, the bacterium is against cefcapene (cefcapene) In another embodiment, the bacterial line is resistant to cefdaloxime. In yet another embodiment, the bacterial line is resistant to cefdinir. In a specific embodiment, the bacteria are held on the head Cefditoren is resistant. In another specific embodiment, the bacterium is resistant to cefixime. In another specific embodiment, the bacterium is cefmenoxime. In another embodiment, the bacterium is resistant to cefodizime. In further embodiments, the bacterium is resistant to cefotaxime. In a further embodiment, the 144087-SP-20091119-1 -124-201019951 bacterial line is resistant to cefpimizole. In one embodiment, the bacterial line is resistant to cephalosporin (ce^) 〇doxime. In another specific embodiment, the bacterial line is resistant to cefteram. In yet another specific embodiment, the bacteria are resistant to cetamine, ceftibuten. In a further embodiment, the bacterium is resistant to ceftiofur. In yet a further embodiment, the bacterial line is resistant to ceftiolene. In one embodiment, the bacterial line is resistant to cefizoxime. In another specific embodiment, the bacteria are resistant to ceftriaxone. In yet another embodiment, the bacterial line is resistant to cefoperazone. In still further embodiments, the bacterial line is resistant to ceftazidime. In one embodiment, a method of treating a patient having a fourth-generation cephalosporin-resistant bacterium comprising administering a compound of formula (V) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the patient is ruminant to the fourth generation cephalosporin. In another specific embodiment, the bacteria are resistant to the fourth generation cephalosporins. In a further embodiment, the bacteria are resistant to cefclidin. In another specific embodiment, the bacterial line is resistant to cefepime. In yet another embodiment, the bacterial line is resistant to cefluprenam. In a specific embodiment, the bacteria are resistant to cefoselis. In another embodiment, the bacterial line is resistant to cefozopran. In another specific embodiment, the bacteria are resistant to cefpirome. In yet another embodiment, the bacterial line is ecsinoquinone 144087-SP-20091119-1 -125-201019951 (cefquinome) is a ruthenium 0. In one embodiment, a treatment with carbenicillin (carbapenem) A method of treating a patient having a drug-resistant bacterium, comprising administering a compound of the formula (V) or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt thereof, stereoisomer, A tautomer or prodrug, wherein the patient is ruminant against carbapenem. In another embodiment, the bacteria are resistant to carbapenem. In a further embodiment, a method of treating a patient having a imipenem-resistant bacterium comprising administering a compound of formula (V) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the bacterial line is resistant to imipenem. In another embodiment, a method of treating a patient having a drug resistant to menotem, comprising administering a compound of formula (V) or a pharmaceutically acceptable salt or ester thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to metopem. In yet another embodiment, a method of treating a patient having a drug resistant to ertapenem, comprising administering a compound of formula (V) or a pharmaceutically acceptable salt or ester thereof A solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial line is resistant to ertapenem. In one embodiment, a method of treating a patient having a resistance to faropenem-resistant bacteria comprising administering a compound of formula (V) or a pharmaceutically acceptable salt, ester or solvent thereof Compound, alkylated quaternary ammonium salt, stereoisomer, 144087-SP-20091119-1 -126-201019951 tautomer or prodrug 'where the bacterial line is resistant to faropenem (faropenem). In another embodiment, the method of treating a patient having a drug resistant to doricanem comprises administering a compound of formula (v) or a pharmaceutically acceptable salt thereof, vinegar, or a solvent. a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug wherein the bacterial line is resistant to dorisenem. In another embodiment, a method of treating a patient having a pampenem-resistant bacterium comprising administering a solvate of formula (v), a cyclized tetra compound or a pharmaceutically acceptable salt, ester, salt, ester, solvate, tautomer or prodrug, ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein the bacterial pair Panipenem is resistant. In yet another embodiment, the method of treating a patient having a drug resistant bacterium, comprising administering a compound of formula (v) or pharmaceutically acceptable thereto, is a method of 胄/α therapy. φ is resistant. Alkylation of quaternary ammonium salts, stereoisomers, wherein the bacterial line is resistant to vancomycin and resistant to vancomycin, and is resistant to vancomycin.

144087-SP-20091119-1 -127- 201019951 Laboratory Standards Society/NCCLS. Performance on Antimicrobial Infectivity Tests t Pre-16th Message Supplement M100-S16. Wayne, PA: CLSI, 2006). The term "minimum inhibitory concentration" (MIC) as used herein refers to the lowest concentration of antibiotic required to inhibit the growth of bacterial excipients in vitro. One of the commonly used antibiotics for the determination of antibiotics is to prepare several & The tube of the serial dilution of the biotin, which is then inoculated with the bacterial monolith of our interest. The MIC of the antibiotic is determined from the tube with the lowest degree of agronomy that does not show turbidity (no growth). A method for treating a patient having a bacterial infection, comprising administering to the patient a compound of the formula (I) or a pharmaceutically acceptable salt thereof, vinegar, a mouthwash, an alkylated quaternary ammonium salt, a stereo Isomers, tautomers or steroidal music' wherein the bacterial infection comprises Staphylococcus aureus which is moderately resistant to vancomycin. In one embodiment, a disease of susceptible bacterium is treated A method of administering the compound of formula 1 or a pharmaceutically acceptable salt thereof, vinegar, solvate, alkylated quaternary ammonium salt, isomer i meta isomer or prodrug Wan Gu Hui : drug resistant, the S. aureus strain has a MIC between about 4 and about 8 micrograms per milliliter. In another specific embodiment, a method of treating bacteria having a bacterium [a method of infecting it includes The patient is administered a compound of the formula (I) or a salt thereof, a vinegar, a solvate, an alkylated quaternary salt, a stereoisomer or a prodrug, wherein The medicinal & anti-drug & S. aureus strain has an MIC of about 4 micrograms per milliliter. In another embodiment, the method of treating a disease having a bacterial infection includes Susceptibility to the compound of formula (I) or its pharmaceutically acceptable 144087-sp-20091119-1 •128· 201019951 Accepted salts, esters, solvates, alkylated quaternary ammonium salts, stereoisomers, tautomerism Or a prodrug, wherein the S. aureus strain having moderate resistance to vancomycin has an MIC of about 5 μg/ml. In a further embodiment, a method of treating a patient having a bacterial infection, It comprises administering to the patient a compound of formula (I) or a pharmaceutically acceptable salt, ester or ester thereof a compound, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the vancomycin s-system with moderate resistance to vancomycin has an MIC of about 6 Micro A/ml. In a further embodiment, a method of treating a patient having a bacterial infection comprising administering to the patient a compound of formula (I), or a pharmaceutically acceptable salt, ester thereof, a solvate, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the Staphylococcus aureus strain having moderate resistance to vancomycin has an MIC of about 7 μg/ml. In one embodiment, a method of treating a patient having a bacterial infection comprising administering to the patient a compound of formula 1 or a pharmaceutically acceptable salt thereof, vinegar, solvate, or alkylation Tertiary ❿ ammonium salt, stereoisomer, tautomer or prodrug, wherein the Staphylococcus aureus strain with moderate resistance to vancomycin has about 8 micro-grams per milliliter. In another aspect, a method of treating a patient having a bacterial infection comprising administering to the patient a compound of formula (I) or a pharmaceutically acceptable salt, ester, solvate thereof, alkylation level 4 An ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the bacterial infection comprises Staphylococcus aureus which is resistant to vancomycin. In a specific embodiment, the Staphylococcus aureus strain resistant to vancomycin has an MIC of between about 16 micrograms per milliliter. In another embodiment, the vancomycin-resistant rhubarb grape halogen system has a MIC of about 2 16 micrograms per 3⁄4 liter. In yet another embodiment, the vancomycin-resistant Staphylococcus aureus strain has a Mic of about 20 micrograms per milliliter. In a further embodiment, the vancomycin strain resistant to vancomycin has an MIC of about 25 micrograms per milliliter. In one aspect, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (II) or a pharmaceutically acceptable salt, ester, solvate thereof, alkylated quaternary ammonium salt thereof , stereoisomers, tautomers or prodrugs, wherein the bacterial infection comprises Staphylococcus aureus with moderate resistance to vancomycin. In one embodiment, a method of treating a patient having a bacterial infection comprises administering to the patient a compound of formula (9) or a pharmaceutically acceptable salt, ester, solvate, alkyl group thereof a quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the vancomycin has a moderate resistance to the S. aureus strain having a MIC of from about 4 to about 8 micrograms per milliliter. between. In another embodiment, a method of treating a patient having a bacterial infection is described in which the patient is administered a compound of the formula or a pharmaceutically acceptable salt thereof, an ester 'solvate, an alkyl group. The quaternary ammonium salt, stereoisomer, substance, tautomer or prodrug has a MIC of about 4 μg/ml for the S. aureus strain with vancomycin and a few drugs. The method of the present invention is a method for treating a disease having a bacterial infection, which comprises administering to the patient a compound of the formula (8) or a pharmaceutically acceptable SB' complex thereof, an alkylated quaternary ammonium salt, a stereo Isomers, ::isomers or prodrugs, wherein the one-color bacterium of the genus Staphylococcus strain with moderate resistance to vancomycin has an MIC of about 5 μg/ml. Further, 144087'sP-2〇〇9i HQ.] 201019951 is a method for treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (π) or a pharmaceutically acceptable compound thereof Accepted salts, esters, solvates, alkylated quaternary ammonium salts, stereoisomers, tautomers or prodrugs, wherein the Staphylococcus aureus strain with moderate resistance to vancomycin has MJC It is about 6 μg/ml. In still a further embodiment, a method of treating a patient having a bacterial infection comprising administering to the patient a compound of formula (11) or a pharmaceutically acceptable salt, ester, solvent, or alkyl group thereof A quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug wherein the S. aureus strain with moderate resistance to vancomycin has an MIC of about 7 micrograms per milliliter. In one embodiment, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (或其) or a pharmaceutically acceptable salt, ester or solvate thereof. A quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the Staphylococcus aureus strain with moderate resistance to vancomycin has a Mic of about 8 μg/ml. In another aspect, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (或其) or a pharmaceutically acceptable sleep, '-ester, solvate, alkylation thereof A quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug wherein the bacterial infection comprises Staphylococcus aureus resistant to vancomycin. In one embodiment, the S. aureus strain having a medicinal property has a MIC of between about 16 micrograms per milliliter. In another embodiment, the vancomycin-resistant Staphylococcus aureus strain has an MIC of about 2 16 micrograms per milliliter. In yet another embodiment, the resistance to vancomycin-resistant Staphylococcus aureus = 144087-SP-20091119-1 -131-201019951 has an MIC of about 20 μg/ml. In a further embodiment, the vancomycin strain resistant to vancomycin has an MIC of about 25 micrograms per milliliter. In one aspect, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (III) or a pharmaceutically acceptable salt, ester, solvate thereof, alkylated quaternary ammonium salt thereof 'Stereoisomer' tautomers or prodrugs which cause bacterial infections including Staphylococcus aureus which is moderately resistant to vancomycin. In one embodiment, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (111) or a pharmaceutically acceptable salt thereof, a solvate, a pharmaceutically acceptable salt, A quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug wherein the vancomycin is resistant to vancomycin and has a Mic of from about 4 to about 8 micrograms per milliliter. between. In another embodiment, a method of treating a patient having a bacterial infection comprising administering to the patient a compound of formula (m) or a pharmaceutically acceptable salt, ester, solvate or alkane thereof A quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the Staphylococcus aureus strain with moderate resistance to vancomycin has an MIC of about 4 μg/ml. In yet another embodiment, a method of treating a patient having a bacterial infection comprising administering to the patient a compound of formula (III) or a pharmaceutically acceptable salt, ester or solvate thereof An alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug wherein the S. aureus strain with moderate resistance to vancomycin has an MIC of about 5 micrograms per milliliter. In the specific embodiment, the method for treating a patient having a bacterial infection comprises administering to the patient a compound of the formula (或其) or a pharmaceutically acceptable salt thereof, 144087-SP-20091119- 1 • 132- 201019951 vinegar, solvates, alkylated quaternary ammonium salts, stereoisomers, tautomers or prodrugs] of which Staphylococcus aureus strains with moderate resistance to vancomycin have It is about 6 μg/ml. In a still further embodiment, the method of treating a patient having a bacterial infection comprises administering to the patient a compound of the formula 111 or a pharmaceutically acceptable salt thereof, a solvent, a compound, An alkylated quaternary ammonium salt, stereoisomer, tautomer or precursor music wherein the Staphylococcus aureus φ with moderate resistance to vancomycin has an MIC of about 7 μg/ml. In one embodiment, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (III) or a pharmaceutically acceptable salt, ester or solvate thereof An alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the Staphylococcus aureus strain having moderate resistance to vancomycin has an MIC of about 8 μg/ml. In another aspect, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of the formula (I) or a pharmaceutically acceptable salt thereof, an oxime ester, a solvate, an alkylation level Ammonium salts, stereoisomers 'tautomers or prodrugs, wherein the bacterial infection includes yellow (iv) globules that are resistant to vancomycin. In a specific embodiment, the Staphylococcus aureus strain resistant to Wancai has an MJC of between about 16 micrograms per milliliter. In another embodiment, the vancomycin-resistant Staphylococcus aureus strain has an MIC of about g16 μg/ml. In yet another specific embodiment, the vancomycin-resistant Staphylococcus aureus strain has an MIC of about 2 G micrograms per milliliter. In the specific embodiment, the MIC of the Staphylococcus aureus strain resistant to the ancient genus has a MIC of about 25 μg/m 144087-sp-20091119-1 -133-201019951 liter. In one aspect, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (IV) or a pharmaceutically acceptable sleep 酽 solvate thereof, an alkylated quaternary ammonium salt, Stereoisomers, tautomers or pre: drugs, wherein bacterial infections include moderate resistance to vancomycin: Staphylococcus aureus. In one embodiment, a method of treating a patient having a bacterial infection includes administering to the patient a compound of formula (III) or a pharmaceutically acceptable salt thereof, vinegar, solvate, or alkylation A salt, a stereoisomer, a tautomer or a prodrug, wherein the S. aureus strain with moderate resistance to vancomycin has an MIC between about 4 and about 8 micrograms per milliliter. In another embodiment, the method of treating a patient having a bacterial infection comprises administering to the patient a compound of formula (IV) or a pharmaceutically acceptable salt, brew, solvate thereof, A quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, having a moderate susceptibility to vancomycin, has an MIC of about 4 μg/ml. In yet another embodiment, the method of treating a patient having a bacterial infection comprises administering to the patient a compound of formula (IV) or a pharmaceutically acceptable salt thereof, a solvate, or a solvate thereof. , an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug wherein the MIC of the Staphylococcus aureus strain having moderate resistance to vancomycin has an MIC of about 5 μg/ml. In a further embodiment, the method of treating a patient having a bacterial infection comprises administering to the patient a compound of formula (IV) or a pharmaceutically acceptable salt thereof: an ester, a solvate, a hospitalization A quaternary salt, a stereoisomer, a tautomer or a prodrug. The golden yellow 144087-sp-20091119-l-134-201019951 Staphylococcus strain with moderate resistance to vancomycin has an MIC of About 6 μg/ml. In still another specific embodiment, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (IV) or a pharmaceutically acceptable scorpion thereof, < cob ester, solvate An alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug, wherein the S. aureus strain with moderate resistance to vancomycin has an MIC of about 7 micrograms per milliliter. In one embodiment, a method of treating a patient having a bacterial infection, comprising administering to the patient

(IV) a compound or a pharmaceutically acceptable salt, ester, solvate, alkyl group thereof; quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof, wherein the vancomycin has moderate resistance The medicinal S. aureus strain has an MIC of about 8 micrograms per milliliter. In another aspect, a method for treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (IV) or a pharmaceutically acceptable salt thereof, hydrazine, solvate, alkylation Grade ammonium salts, stereoisomers, tautomers or prodrugs wherein the bacterial infection comprises yellow grape ball 8 which is resistant to vancomycin. In a specific embodiment, the vancomycin-resistant Staphylococcus aureus strain has a MIC of about 16 micrograms per milliliter. In another embodiment, the vancomycin-resistant golden yellow grape The cocci line has an MIC of about $16 microgram/ml. In yet another specific embodiment, the vancomycin-resistant Staphylococcus aureus strain has an MIC of about 20 micrograms per milliliter. In a further embodiment, the S. aureus strain resistant to phylum has a MIC of about 25 micrograms per milliliter. In one aspect, a method for treating a patient having a bacterial infection, comprising 144087-sp-20091 119-1 -135-201019951::: a patient administering a compound of formula (v) or a pharmaceutically acceptable salt thereof , vinegar, refrigerant a, alkylated tetra-precursor, wherein the bacterial isomer or golden @ infection with moderate resistance to vancomycin, Staphylococcus aureus. In a library and planting a disease from / i bacterial infection, in the case of a treatment with or without a 'method', which comprises administering to the patient a salt of the formula (v), vinegar, vinegar, a solvate, an alkylated quaternary salt, a di-structure, a tautomer or a prodrug, which has a resistance to the phylogenetic Staphylococcus aureus strain of about 4 to about 8 micrograms. In the specific embodiment, the method for treating a patient having bacteria:-: includes administering to the patient a compound of the formula (V) or a salt thereof, a vinegar or a solvent. Physicochemical, tertiary, salt, stereo, 'structure, tautomer or prodrug, #中中的resistant resistance to Staphylococcus aureus strain with MIC of about 4 μg / ml . Further, in a specific embodiment, a method for treating a disease having a bacterial infection comprises administering to the patient a compound of the formula (V) or a pharmaceutically acceptable salt, ester, solvate or alkylate thereof. Grade ammonium salts, stereoisomers, t-isomers or prodrugs, wherein the S. aureus strain with moderate resistance to vancomycin has an MIC of about 5 micrograms per milliliter. In a further embodiment, a method of treating a patient having a bacterial infection comprising administering to the patient a compound of formula (V) or a pharmaceutically acceptable salt thereof, s曰/glutactate, alkane The quaternary ammonium salt 'stereoisomer, tautomer or steroid drug, wherein the Staphylococcus aureus strain with moderate resistance to vancomycin has an MIC of about 6 μg/ml. In still a further embodiment, a method of treating a patient having a bacterial infection comprising administering to the patient 144087-sp-20091119-l-136-201019951 the compound of formula (v) or a pharmaceutically acceptable compound thereof a salt, a hydrazine, a dimer, an alkylated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the S. aureus strain having moderate resistance to vancomycin has an MIC of about 7 μg/ml. In one embodiment, a method of treating a patient having a bacterial infection, comprising administering to the patient: • (v) a compound or a pharmaceutically acceptable salt, ester or solvent thereof , alkyl 1 quaternary ammonium salt, stereoisomer, tautomer or prodrug, which has a moderate resistance to vancomycin, the golden yellow grape g system has an MIC of about 8 μg / ML. In another aspect, a method of treating a patient having a bacterial infection, comprising administering to the patient a compound of formula (v) or a pharmaceutically acceptable salt thereof, a guanidine, a solvate, an alkylation level Ammonium salts, stereoisomers, tautomers or prodrugs wherein the bacterial infection includes Staphylococcus aureus which is resistant to vancomycin. In one embodiment, the vancomycin-resistant Staphylococcus aureus strain has a MIC between about 16 micrograms/ml. In another embodiment, the resistance to vancomycin is gold. The Staphylococcus aureus strain has an MIC of about $16 μg/ml. In yet another specific embodiment, the Staphylococcus aureus strain resistant to vancomycin has an MIC of about 20 micrograms per milliliter. In a further embodiment, the S. aureus strain resistant to phylum has a MIC of about 25 micrograms per milliliter. Enterococci, which are resistant to vancomycin, are bacteria that are normally found in human intestines and female reproductive tracts, and are often found in this environment. These bacteria sometimes cause a feeling 144087-SP-20091119 -1 -137- 201019951 Dyeing. In some cases, Enterococcus has become resistant to vancomycin (also known as vancomycin-resistant Enterococcus or VRE). A common form of resistance to vancomycin occurs in the collection of a group of enterococci that encode a gene encoding a peptidoglycan precursor to incorporate D-Ala-D-Lac in place of D. -Ala-D-Ala » The six different types of vancomycin resistance shown by Enterococcus are: Van_A, Van B, Van_c, Van D, Van-E and Van-F. In some cases, Van_A VRE is resistant to both vancomycin and ticlosin, while in other cases, VanBVRE is resistant to vancomycin but sensitive to ticlosin; In further cases, the Van-C moiety is resistant to vancomycin and sensitive to ticlosin. The invention relates to a method for treating a patient having vancomycin & Enterococci, which comprises administering to the patient a compound of formula 1 or a pharmaceutically acceptable salt or ester solvate thereof , alkylated quaternary ammonium salts, stereoisomers, tautomers or prodrugs, #中Enterococcus has developed resistance to vancomycin. In one embodiment, the patient has been previously treated with vancomycin for a sustained period of time. In another specific embodiment, the patient has been hospitalized. In yet another embodiment, the disease string has a weakened immune system, such as a patient in an intensive care unit or in a cancer or transplant ward. In the specific embodiment, the patient has undergone a surgical procedure such as abdominal or chest surgery. In a further embodiment, the patient has been transplanted. In a specific embodiment, the patient has a medical device so that the infection has developed. In another specific embodiment, the medical device is a catheter or a central intravenous (IV) catheter. 144087-sp-20091119-1 -138- 201019951 Wan Guhui: Susceptible (I) and topographical four, in which vancomycin is administered by formula (I) and hospitalized four. Intestinal spheres, in another embodiment, are a method of treating a patient having a drug-resistant Enterococcus genus, which comprises the compound of the disease or a pharmaceutically acceptable salt, ester or solvent thereof, Stereoisomers, tautomers or precursors: the genus has a Van-A resistance.

In another embodiment, a method of treating a patient having a genus resistant to Enterococcus is included, which comprises the compound of the disease or a pharmaceutically acceptable salt thereof, a vinegar, a solvent, an ammonium salt, a stereo The construct, tautomer or prodrug genus has Van-B resistance. In another embodiment, the method of treating a patient having a drug-resistant Enterococcus genus, comprising administering to the patient a compound of Formula 1, or a pharmaceutically acceptable salt thereof, §, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug wherein Enterococcus has Van-C resistance. In one aspect, a method for treating a patient having a resistance to vancomycin-resistant Enterococcus, comprising administering to the patient a compound of the formula (π) or a pharmaceutically acceptable salt thereof, a solvent, a solvent Compounds, alkylated quaternary ammonium salts, stereoisomers, tautomers or prodrugs of the genus Neisseria gonorrhoeae have developed resistance to vancomycin. In one embodiment, the patient has been previously treated with vancomycin for a sustained period of time. In another specific embodiment, the patient has been hospitalized. In yet another specific embodiment, the patient has a weakened immune system' such as a patient in an intensive care unit or in a cancer or transplant ward. In a further embodiment, the patient has undergone surgery 144087-sp-20091119-l-139-201019951 procedures, such as abdominal or chest surgery. In addition, the patient has been transplanted by VRE. In the "Well" _ & . 'in the specific embodiment' the patient has a medical condition that has been transplanted by VRE. In the specific embodiment / device ' so that infection has developed. In another catheter with a catheter or a central venous σν). In the case of the case, medical equipment

In another embodiment, a method of treating a patient suffering from a drug-resistant Enterococcus genus comprises administering a compound to a vancomycin compound or a pharmaceutically acceptable rose, sputum patient (II) Ammonium 豳, 俨 俨 椹 椹 θ solvate, alkylated quaternary liCjru stereoisomer, tautomer 忐 & genus has Van-eight resistance. (4) The substance or the body drug, wherein the enteric ball is in another specific embodiment. The method is a method for treating a patient suffering from a drug-resistant Enterococcus, a savancomycin compound or a pharmaceutically acceptable compound thereof. The patient is administered a helium-integrated isomer, tautomer or prodrug, wherein Enterococcus has Van-B resistance. Re-intestinal globule: another embodiment is a method of treating a patient having a genus of vancomycin, which comprises the compound or a pharmaceutically acceptable hydrazine, _ The sulphate, the solvate, the alkylated quaternary ammonium salt, the stereoisomer, the tautomer or the prodrug genus have Van-C resistance. The 肠T enteric sphere is, in one aspect, a method of treating a patient having a bacterium belonging to the genus Enterococci which is resistant to vancomycin, which comprises administering to the patient a compound of the formula or a medicinal herb thereof. Solvates 'alkylated quaternary ammonium salts, stereostructures, tautomers or prodrugs, and the genus Enterococcus genus has developed resistance to phylogenetic. In the specific implementation of the project, the patient has been in the first, month y 144087-sp-20091119-l • 140- 201019951 treated with vancomycin for a sustained period of time. In another specific embodiment, the patient has been hospitalized. In yet another embodiment, the diseased string has a weakened immune system' such as a patient in an intensive care unit or in a cancer or transplant ward. In a further embodiment, the patient has undergone a surgical procedure, such as abdominal or chest surgery. In a further embodiment, the patient has been transplanted by VRE. In the specific embodiment, the patient has medical care

The device is so developed that the infection has developed. In another embodiment, the medical device is a catheter or a central intravenous (IV) catheter. In another embodiment, the method of treating a patient having a drug-resistant Enterococcus genus, comprising administering to the patient a compound of the formula or a pharmaceutically acceptable bee thereof,护•no· ig, bath medicinal compound, quaternary ammonium salt, stereoisomer, and interconversion show this Wenwu structure or body music, in which Enterococcus has Van-A resistance. In another embodiment, the method for treating a patient having a genus of the genus: a genus of the genus, includes administering the _ _ _ _ _ Accepted salts, _, solvates, alkylated tetra-salt stereoisomers, tautomers or prodrugs, wherein Enterococcus has Van-B resistance. r = in the intestinal example is a treatment having a compound for vancomycin or a pharmaceutically acceptable composition thereof comprising the administration of the patient (i.e., grade salt, stereoisomer, = salt, 8 days, solvent) The compound, the genus of the genus, has an ic anti-dimer, a tautomer or a prodrug, wherein the intestinal tract is treated on the one hand and has the resistance to the genus Enterococcus 144087-SP-20091119- 1 - 141 - 201019951; "" method comprising administering to the patient a compound of formula (iv) or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt thereof, stereo Isomers tautomers or 4-body drugs, of which Enterococcus has developed resistance to vancomycin. In a specific embodiment, the patient has been treated with vancomycin for a while. In another embodiment, m is hospitalized. In yet another embodiment, the diseased string has a weakened immune system, such as in an intensive care unit or in a cancer or transplant ward. In the specific example t, the patient has undergone a surgical procedure, such as the abdomen or chest In a specific embodiment, the patient has been transplanted. In one embodiment, the patient has a medical device so that the infection has developed. In another specific embodiment, the medical device is a guide Uterine or central venous (Iv) catheter. Another method for the treatment of patients with a disease of the genus Escherichia and the drug-resistant enterococci, including the patient (3) The compound or its pharmaceutically acceptable salt, hydrazine, solvate, alkylated quaternary salt, stereoisomer, tautomer or prodrug has Van-A resistance. In another specific embodiment, the method for treating a patient having a drug-resistant Enterococcus genus, the scorpion, the sulphate, the saponin, the tautomer, the tautomer or the sputum The genus has a Van-B resistance. In another specific embodiment, the method is a method for treating a patient having a drug-resistant Enterococcus, which includes, Susceptible administration of formula (IV) 144087-SP-20091119-1 -142- 201019951 compound or its pharmaceutically acceptable a salt, an ester, a solvate, a thiolated quaternary ammonium salt, a stereoisomer, a tautomer or a prodrug, wherein the intestinal genus has Vm-C resistance.

In one aspect, a method of treating a patient having a resistance to vancomycin-resistant Enterococcus: comprising administering to the patient a compound of formula (v) or a pharmaceutically acceptable salt, brew, or solvate thereof , alkylated quaternary ammonium salts, stereoisomers, tautomers or prodrugs wherein the Enterococcus genus has developed resistance to vancomycin. In the specific embodiment, the patient has been previously treated with vancomycin for a sustained period of time. In another specific embodiment, the patient has been hospitalized. In yet another embodiment, the patient has a weakened immune system, a disease in the intensive care unit or in a cancer or transplant ward. In a specific embodiment, patient 6 performs a surgical procedure, such as abdominal or chest surgery. In a further embodiment, the patient has been transplanted by VRE. In a specific embodiment, the patient has a medical device so that the infection has developed. In another embodiment, the medical device is a catheter or a central intravenous (IV) catheter. In another embodiment, a method of treating a patient having a genus of the genus Intestinal Sphere®, comprising administering to the patient a compound of formula (V) or a pharmaceutically acceptable compound thereof a salt, a solvate, a salt, a stereoisomer, a tautomer or a prodrug, wherein the Enterococcus has Van-A resistance. In another embodiment, the method of treating a compound of the genus Enterococcus is a compound or a pharmaceutically acceptable salt thereof, or a serotherapy having a vancomycin, which comprises administering to the patient ( ν) 酉曰, solvate, alkylation 144087-sp-20091119-1 -143· 201019951 class salt, stereoisomer, tautomer or prodrug has Van-B resistance. In another embodiment, a method for treating a patient having a genus of genus and a drug resistant enterococci, and administering a compound of the formula (V) to the patient Or a pharmaceutically acceptable hydrazine thereof, which is present in the form of a solvate, an alkylate salt, a stereoisomer, a tautomer, or a prodrug, wherein the enterococci The genus has Van-C resistance. [Embodiment] EXAMPLES The following is a detailed description of the synthesis, properties and activities, and applications of the peptides prepared herein. It should be understood that the following is only representative. Example 0 Example 1 Synthesis of compound (1)

Vancomycin (30 g) was slowly added to the mixed solution (300 ml "TFA · H^O = 9:1" at 10 °C. Then the reaction mixture was taken at 1 Torr. (2) was given for 2 hours (and the progress of the reaction was confirmed by HPLC). The reaction mixture was allowed to float in 1500 ml of cold diethyl ether, filtered, dried, and washed with a few times by a key and dried under vacuum. The crude product was purified by reverse phase column chromatography (MeCN: H.sup..sup.sup.sup.sup.sup.sup.sup.sup. (2) Synthesis

The compound (2) was prepared by using a procedure similar to the preparation of the compound (1) and replacing vancomycin with demethyl vancomycin. Example 3 Synthesis of Compound (3)

❿ A procedure similar to the preparation of the compound (1) was used, and vancomycin was replaced with LY264826 to prepare a compound (3). Example 4 Synthesis of Compound (4)

144087-SP-20091119-1 -145-201019951 A compound (4) was prepared by using a procedure similar to that of the compound (1), and replacing vancomycin with erirammycin. Example 5

Compound (1) (5.0 g, 3.72 mmol) was dissolved in (35 mL / 35 mL). Then, τεΑ (0·77 ml, 5.58 mmol) was added to cool the reaction mixture down to hunger, followed by slowly adding _) 2 〇 gram, sample millimolar). After the addition, the reaction mixture was hunger (four) for 7 hours. It was concentrated and the crude material was purified by reverse phase column (MeCN: % 〇 = 1:5 3: ι). 3 g of the compound (5) was obtained as a white solid (yield = 6 %). Example 6

The compound (6) is prepared by using a procedure similar to the preparation of the compound (5), and substituting the compound (2) for the compound (1). Example 7 144087-sp-20091119-1 -146- 201019951 Synthesis of Compound (7)

The compound (7) is prepared by using a procedure similar to the preparation of the compound (5), and substituting the compound (3) for the compound (1).

Example 8 Synthesis of Compound (8)

The compound (8) is prepared by using a procedure similar to the preparation of the compound (S) and substituting the compound (4) for the compound (1).

Example 9

The compound (9) was prepared by using a procedure similar to the preparation of the compound (5), and substituting vancomycin 144087-sp-20091119-l-147-201019951 (1). Example 10 Synthesis of Compound (10)

The compound (10) was prepared by using a procedure similar to the preparation of the compound (5), and substituting the compound (1) with deacetyl vancomycin. Example 11 Synthesis of Compound (11)

Compound (5) (1 g, 0.712 mmol) and 2-adamantylamine hydrochloride (4 g. DIEA was added to the solution to adjust the pH of the reaction mixture to 8. Then, in the presence of DIEA, HATU (0.3 g, 0.789 mmol) was added. Stirring was continued for about 1 hour. The progress of the reaction was confirmed by TLC to completion. Next, the resulting mixture was added to 120 ml of water and filtered. The filter cake was washed twice with water and dried in vacuo. Purification by a normal phase tantalum column (MeOH: CH2Cl2 = 144087-sp-20091119-1 -148-201019951 1:7-1:3) afforded compound (11) as a white solid (850 mg, yield =77%) Example 12 Synthesis of Compound (12)

The compound (12) is prepared by using a procedure similar to the preparation of the compound (11), and substituting the compound (6) for the compound (5). Example 13 Synthesis of Compound (13)

Boc

The compound (13) is prepared by using a procedure similar to the preparation of the compound (11), and substituting the compound (7) for the compound (5). Example 14 Synthesis of Compound (14) 144087-SP-20091119-1 -149- 201019951

The compound (14) is prepared by using a procedure similar to the preparation of the compound (11), and substituting the compound (8) for the compound (5). Example 15

Synthesis of Compound (15)

The compound (15) is prepared by using a procedure similar to the preparation of the compound (11), and substituting the compound (9) for the compound (5). Example 16 Synthesis of Compound (16)

Using a procedure similar to that of the compound (11), and substituting the compound (10) for 144087-SP-20091119-1 150· 201019951 (5), the compound (16) was obtained. Example 17 Synthesis of Compound (17)

TFA (0.5 mL) was added dropwise to a suspension of compound (11) (380 mg) in EtOAc. The reaction mixture was stirred at 〇t: for 1 hour and then at room temperature for another hour. The reaction was followed by hpLC until ether (3 mL) was added and the solid formed was collected and washed twice with ether. The collected white solid was dried and purified by preparative HPLC to give compound (17) as a TFA salt. Example 18

Synthesis of Compound (18)

A procedure similar to the preparation of the compound (17) is used, and the compound (11) is substituted with the compound (12), and the compound (18) is made of an XFA salt. Example 19 Synthesis of Compound (19) 144087-sp-2009l 119-1 -151- 201019951

A procedure similar to the preparation of the compound (17) is used, and the compound (11) is substituted with the compound (13), and the compound (19) is made of a TFA salt. Example 20 Synthesis of Compound (20)

❹ A procedure similar to the preparation of the compound (17) is used, and the compound (11) is substituted with the compound (14), and the compound (20) is made of a TFA salt. Example 21 Synthesis of Compound (21)

A procedure similar to that of the compound (?7) was used, and the compound (11) was replaced with the compound (15), and the compound (21) was prepared as a TFA salt. Example 22 144087-SP-20091119-1 -152· 201019951 Alternative Synthesis of Compound (21)

Add 2-adamantylamine hydrochloride (20.0 g), DIPEA (35.0 g) and HATU to a solution of vancomycin hydrochloride (100.0 g) in DMSO (800 mL) at ambient temperature. 28.1 g) and stir. The reaction mixture was stirred overnight. Analytical HPLC showed the reaction was completed. The DMSO was removed under vacuum. The residue was purified by reverse phase column chromatography (C18 silica gel, CH3CN-H20: 5%-30%). The collected fractions were concentrated to afford compound (21) (45 g) as white powder.

Example 23

A procedure similar to the preparation of the compound (17) is used, and the compound (11) is substituted with the compound (16), and the compound (22) is made of a TFA salt. Example 24 Gasification of 4-(pentyloxy)benzene-1- sure 醯A·phenol (28.2, 0.3 mol, 1 eq.), potassium carbonate (63 g, 1.5 eq.) 144087-SP-20091119-1 -153 - 201019951 and a mixture of 1-bromopentane (47.6 g) in acetone (200 ml) were stirred overnight under reflux. The solid was filtered off. The filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (300-400 mesh, eluting solvent: hexane) to afford pentyloxybenzene (45 g, 90%) as colorless oil. B. Addively chlorosulfonic acid (70 g, 2 equivalents) in a solution of pentyloxybenzene (41 g, 1 eq.) in CH2C12 (300 mL: liters) at -1 °C The solution in CH2C12 _ (50 mL) was stirred. After completion of monitoring by Tlc (EtOAc/hexane = 1/10), the reaction mixture was poured into ice-water mixture (5 g). The organic layer was subjected to liquid separation treatment. The aqueous layer was extracted with CH2C12. The combined organic phase was washed with brine and dried over NaaSO4, concentrated under reduced pressure, and purified by column chromatography (300-400 mesh, solvent:hexane) to obtain vaporized 4-(pentyloxy) Benzene-1-sulfonate (42 g, 60%) with a yellow oil. Example 25 Gasification of 4_Butoxybenzene_ι·Accord at 〇°C 'Addition of concentrated sulfuric acid in a mixture of 40% aqueous hydrobromic acid solution (76 g) and n-butanol (18.5 g) (12.5 g) and stir. The reaction 喾 mixture was heated under reflux for 5 hours and then atmospheric distillation was applied. The collected liquid was dissolved in ether' and washed with diluted sodium bicarbonate. The ether layer was dehydrated & dried and concentrated to afford 1-methanol hexane (24 g, 69%) as a colourless oil. 1 H NMR (400 Μ), 7.9 (2Η, d, Ar), 7.0 (2H, d, Ar), 4.0 (2H, t, -CH2-), 1.8 (2H, m), 1.4 (4H, m) , 0.8 (3H). A mixture of the desired (17.3 g), carbonic acid (48 g) and l-bromobutane (24 g) in acetone was stirred at reflux overnight. Get out of the solid. The filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on EtOAc EtOAc (EtOAc) At _10.匚144087-sp-20091119-1 -154- 201019951, in a solution of butoxybenzene (25 g) in CH2 % (2 mL), add gas-based sulfonic acid (40 g) in αίβΜκκ ) The solution in ml) and stir. After completion of monitoring by TLC (Et?Ac / [calc. = 1/10), the reaction mixture was poured into ice water mixture (300 g). The organic layer was subjected to liquid separation treatment. The aqueous layer was extracted with cH2Ci2. The combined organic phases were washed with brine, dried over Na2SO 4 and evaporated, evaporated, evaporated, evaporated, 4_ Butoxybenzene 4 continued (19 g, 46%) with a yellow oil. Example 26 Gasification of 4-(hexyloxy)benzene small brewing Using a procedure similar to that of Example 25, hexanol was used instead of n-butanol to prepare 4-(hexyloxy)benzene-1-methyl chloride. Example 27 Gasification of 4-propoxybenzene_1_Confirmation Using a procedure similar to that of Example 25, using propanol instead of n-butanol to make 4-propoxybenzene-1-chlorobenzene. Example 28 (3. decyloxypropoxy)benzene at room temperature in phenol (4.7 g, 63.2 mmol) with K2C 〇3 powder (26 g '186 mM) in N,N-dimethyl Add 1,3-dibromopropane (20 ml, 186 mmol) to the suspension in carbamide (1 mL) and stir. The reaction mixture was heated at 50 °C for 5 hours and monitored by TLC until disappear. The reaction mixture was quenched by the addition of water (200 mL) and evaporated. The combined organic phases were dehydrated and dried with Na2SO4 and concentrated on a rotary evaporator by 144087-SP-20091119-1 -155-201019951 to obtain (3-bromopropoxy)benzene and several removal products. a mixture. (3-Bromopropoxy)benzene (6.2 g, 48%) was obtained by vacuum distillation. 1H NMR (CDC13, 400 MHz), 2.3 (2H), 3.6 (2H), 4.1 (2H), 6.85-6.95 (3H), 7.3 (2H); 13C NMR (CDC13, 400 MHz) 59, 67, 71, 114, 120, 129, 158). (3-Bromopropoxy)benzene (9.2 g, 42.8 mmol) was added dropwise in a solution of NaOMe in methanol (in situ from 1.1 g of sodium dissolved in 200 mL of MeOH). A solution of ML in MeOH. After the addition was completed, the reaction mixture was stirred under reflux overnight until the starting material disappeared. The volatile solvent was removed by a rotary evaporator under vacuum. (3-Methoxypropoxy)benzene (4.7 g, 66%) was obtained by vacuum distillation. Made of ^NMI^CDClh 400 MHz) 3.45 (3H), 3.75 (2H), 4.12 (2H), 6.95 (2H), 7.3 (2H) ; 13 C NMR (CDC13,400 MHz) δ 59, 67, 71,114,120,129,158 ° Example 29 (3-Ethoxypropoxy)benzene in NaOEt (from 1.1 g of sodium dissolved in 200 ml of EtOH) was added dropwise (3-bromopropoxy)benzene (9.2 g) , 42.7 millimoles) in 20 ml of EtOH. After the addition was completed, the reaction mixture was stirred at reflux overnight until the starting material disappeared. The volatile solvent is removed by a rotary evaporator under vacuum. (3-Ethoxypropoxy)benzene (4.7 g, 60%) was isolated by vacuum distillation. 1H NMR (CDC13, 400 MHz), 1.25 (3H), 2.1 (2H), 3.55 (2H), 3.7 (2H), 4.2 (2H), 4.15 (2H), 6.95-7.05 (4H), 7.3-7.4 ( 2H), 13C NMR (CDCI3, 400 MHz) 15.2, 29.9, 64.3, 65.2, 66.3, 114.5, 120.6, 129.4, 159.0. Example 30 144087-sp-20091119-l 156-201019951 (3-propoxypropoxy)benzene Using a procedure similar to that of Example 29, (3-propoxypropoxy)benzene was prepared by using n-propanol instead of ethanol. 1H NMR (CDC13, 400 MHz) 0.8 (3H), 1.4-1.6 (2H), 1.9-2.0 (2H), 3.2-3.3 (2H), 3.5-3.6 (2H), 3.9-4.1 (2H), 6.7- 6.9 (2H), 7.1-7.2 : (2H) 〇 Example 31 Gasification 4·(3-propoxypropoxy)benzene-1_ylindole^(3-propoxypropoxy)benzene (1.52 Gram, 10 mmol) in 40 ml of tetrahydrofuran (THF) in hydrazine. A solution of gas sulfonic acid (4 gram '% mM) in dichloromethane was added dropwise under stirring and stirred rapidly under nitrogen. The reaction mixture was stirred at room temperature for 45 minutes and poured into cooled water. Extracting, washing, dehydrating and drying, and concentrating to obtain a slurry, which is separated by a flash column chromatography on a silica gel to provide a gasification of 4_(3_propoxypropoxy)benzene (1 g) 37%). iHNMR (CDCl3, 400 MHz), 0.8 (3 Η), 1.5-1.6 (2 Η), 2.0-2.1 (2H), 3.25-3.35 (2H), 3.5-3.6 (2H), 4.1-4.2 (2H), 6.9- 7.0 (3H), 7.8-7.9 ❹ (2H). Example 32 Gasification of 4-(3-methoxypropoxy)benzene as a small-scale procedure Using a procedure analogous to Example 31, using (3-methoxypropoxy)benzene instead of (3-propoxypropoxy)benzene , made of 4_(3-methoxypropoxy)benzene chlorinated. Example 33 Gasification of 4·(3-ethoxypropoxy)benzene-1-ylhydrazine Using a procedure similar to that of Example 31, using 3-ethoxypropoxybenzene instead of (3-propoxypropoxy)benzene , made of chlorinated (3_ethoxypropoxy) benzene succinct. 144087-SP-20091119-1 -157-201019951 Example 34 (2-Ethoxyethoxy)benzene In a 500 ml round bottom flask, EtOH (150 mL), phenol (15.4 g) was added sequentially at 0 °C. ), K2CO3 (10.7 g) and ethylene oxide (1 ml), and stirred. The resulting mixture was allowed to warm to room temperature and stirred overnight. The reaction was monitored by GC-MS&apos; and when the reaction was completed, 200 ml of di-methane was added to the reaction mixture. The crude product was passed through a pad of Shixia to remove insoluble solids. The organic phase was concentrated under vacuum. The residue was separated by distillation under reduced pressure to give 2-phenoxyethanol (17.75 g) as an oil. Powdered NaH (2.7 g, 60% in mineral oil) was added to a solution of 2- oxoethanol (7 g) in 40 mL THF at room temperature and was applied. The resulting mixture was stirred at room temperature for 1 hour, then ethyl bromide (4 mL) was added and stirred for an additional 2 hr. The reaction was monitored by TLC (hexane: EtOAc = 10:1). </ RTI> 1 liters of ice water was added to the reaction mixture. The organic layer was separated. The aqueous layer was extracted with EtOAc (2×20 mL). The combined organic phases were washed with brine, dried over Na Naz~ The residue was purified by flash column chromatography (solvent: hexanes) eluted eluted eluted elute Example 35 (2-propoxyethoxy)benzene was prepared using a procedure similar to that prepared for (2-ethoxyethoxy)benzene in Example 34 and replacing ethyl bromide with 1-. Propoxyethoxy)benzene. Example 36 Gasification 4·(2·ethoxyethoxy)benzene-1-n- 醢 144087-SP-20091119-1 -158- 201019951 Using a procedure similar to that of Example 24 A, regarding gasification of 4_(pentyloxy) The preparation of benzene was carried out, and pentyloxybenzene was replaced with (2-ethoxyethoxy)benzene to give 4-(2-ethoxyethoxy) chloroformate. Example 37 Gasification of 4-(2-propoxyethoxy)benzene Small Stuff: Using a procedure similar to that of Example 24 A, for the preparation of gasified 4-(pentyloxy)benzene sulfonate, and (2) -Propoxyethoxy)benzene is substituted for pentyloxybenzene to give a vaporized 4-(2-ethoxyethoxy) stupid. Example 38 N_(2-Aminoethyl)-4-(pentyloxy)benzene acetal at 〇 °c in ethane-I,2-diamine (8.5 g) in CH2Cl2 (50 mL) To the solution, a solution of 4-butoxybenzene chlorinated (4 g) in DCM (1 mL) was slowly added dropwise and stirred. After stirring at room temperature for 35 hours, the reaction mixture was washed with saturated NH4Cl. The organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure and purified by EtOAc EtOAc EtOAc EtOAc White powder. Example 39 N-(6-Aminohexyl)_4-(pentyloxy)benzene acetal at 0 ° C in hexane-1,6-diamine (8.8 g) in CH2C12 (40 mL The solution in the solution was slowly added dropwise to the solution of 4-butoxybenzene sulfonate (2 g) in DCM (20 mL) and stirred. After stirring at room temperature for 4 hours, the reaction was carried out. The mixture was washed with saturated NH.sub.4Cl.sub.sub.sub.sub.sssssssssssssssssssssssssssssssssssssssssssssssssss Amine (2 g) as a white material. 144087-SP-20091119-1 -159-201019951 Example 40 4_Amino-N-(4-(pentyloxy)benzenesulfonyl)butanamine Hydrochloric acid A solution of 4-aminobutyric acid (10.3 g) in THF (100 mL) was combined with a solution of K.sub.3 (3 g) in water (50 mL). Vinegar (26 g) was added dropwise to the mixture and stirred at room temperature The resulting mixture was stirred at room temperature and monitored by TLC until the starting material was completely consumed. THF was removed under reduced pressure and the residual aqueous phase was adjusted with aqueous solution (1 N) ρ Η = 4·5, extracted with Et 〇Ac, washed with brine, dried over MgSO 4 and dried to afford 4-(tris-butoxyamino)butyric acid (19.6 g &apos; 96%). DCC (1.59 g) and HOSu (0.88 g) were added to a solution of 4-(t-butoxycarbonyl)butyric acid (1 737 g) in DMF (20 mL) and stirred. The mixture was warmed to room temperature and stirred overnight. The starting material disappeared by TLC. The solid formed was filtered and washed with a small portion of DMF. At room temperature, containing 2,5 diketotetrahydropyrrole-1 To the filtrate of the base (tris-butoxycarbonylamino)butyrate, 4-(pentyloxy)benzenesulfonamide (2 g) was added and stirred. The mixture was stirred and monitored by TLC until The starting material disappeared. The solid formed was removed by filtration under vacuum. The filtrate was poured into water (2 mL) and the organic layer was separated. The aqueous layer was extracted with EtEAc. The combined organic layers were washed with water and brine, and then dried in anhydrous water. After concentration under reduced pressure, the second-butyl 4-keto group was obtained. 4-(4-(pentyloxy)phenyl decylamine) butyl carbamate as a slurry. The slurry was dissolved in 1 mL of Et〇Ac and HCl was used at 0 C (made in methanol) 1 〇 ml of gasified acetonitrile) was treated on the spot. Upon completion of the reaction, the solvent was removed under reduced pressure. The residue was dissolved in 144087'Sp-20091119-1 201019951 20 ml of water. The aqueous solution was washed with Et 〇Ac (2 χ 1 mL) and adjusted to pH = 8 with a saturated aqueous K: 2 C 〇 3 solution. Extracted with Et 〇Ac, washed with brine, dried over NazSO4, and concentrated under reduced pressure to afford 4-amino-(n-((oxy) phenylsulfonyl)butanamine hydrochloride (5 〇 〇mg), as a white solid. Example 41 2·Amino.Ν·(4·(pentyloxy)benzenesulfonyl)acetamide hydrochloride salt DCC (5 g, 28.5 mmol) with HOSu (3.83) under nitrogen and at room temperature g g, 30 mmol) was added to a solution of 2_(t-butoxycarbonylamino)acetic acid (5 g, 28 5 mmol) in DMF (65 mL). The reaction mixture was stirred for 12 hours. The DMF was removed under reduced pressure by an oil pump. The residue was treated with dichloromethane. The insoluble solid was filtered off by filtration under reduced pressure. The filtrate was concentrated by a rotary evaporator to provide 6.8 g of 2-(tris-butoxycarbonylamino)acetic acid 2,5-di-tetrahydrop-pyryl acetate as a white powder in 87% yield. . 2,(Third-butoxycarbonylamino)acetic acid 2,5-dionetetrahydropyrrole-yl (2 58 g, 9.6 house mole), 4-(pentyloxy)benzene decylamine (2.4 g, 9.6 mmol) and a mixture of EtOAc (EtOAc, m. After the reaction was completed, the reaction mixture was poured into ice water. • Extracted with EtOAc (2×50 mL), washed with brine (2×50 mL), dried over Na 2 SO 4···················· (Pentyloxy)phenyl decylamino)ethylamino decanoic acid tert-butyl ester as a white powder. Treatment of 3-keto-2-(4-(pentyloxy)phenylphosphonium)ethylaminocarbamic acid tert-butyl ester (4 g '10 mmol) in 4N HCl in methanol. It was stirred at room temperature for 30 minutes. When the reaction was completed, the solid 2-amino-N-(4-(pentyloxy)benzene sulfonyl) acetamide hydrochloride (2 g, 9 %) was collected by filtration under reduced pressure. 144087-SP-20091119-1 -161 - 201019951 Example 42 2_(Hexyloxy)acetic acid Sodium hydride (16.8 g, 35 eq.) was added to 1-hexanol (22.5 g) under EtOAc. 1.1 equivalents in a mixture with THF (100 ml) and stirred rapidly. Upon completion of the addition, the reaction mixture was allowed to warm to room temperature and stirred for an additional 4 hours. (: Next, a solution of 2-bromoacetic acid (1 eq.) in _ was added dropwise to the reaction mixture. The reaction mixture was allowed to warm to room temperature and stirred under reflux overnight. The volatile solvent was removed, the residue was washed with hexanes, then dissolved in sputum, and adjusted to pH = 4 by addition of aqueous HCl (2 N). extraction, dehydration, and concentration to obtain 2-( Hexyloxy)acetic acid (28 g), a colorless oil, 88% yield. 1 hnmr (4 () 〇 MHz, CDC13): 〇.7 (3H), U-1.3 (6H), 1.6 (2H), 3.4 (2H), 4(2H), 1〇.5(1Η); 13CNMR (400MHz, CDC13): 13,22,25,29,31,67,71,175. Example 43 2,5-dione 4 Hydrogen pyrrolidinyl 2-(trimethyldecyl)ethyl carbonate is added dropwise in a solution of triphosgene (25 g, 0.5 eq.) in THF (200 mL). a mixture of methyl mercapto)ethanol (20 g, hydrazine equivalent) and TEA (25 ml '1.1 eq.) in THF. After stirring at room temperature for 2 hours, HOSu (1 eq.) at 〇 ° C A solution of THF (50 mL) was added to the reaction mixture. The mixture was stirred overnight. The solid formed was removed by filtration under reduced pressure. The filtrate was treated on a silica gel column, eluted via CH2%. The collected fractions were concentrated to a volume of 10 ml and poured. In pure hexane, the precipitated solid 2,5-dionetetrahydropyrrole small 2-(trimethyldecyl)ethyl carbonate was collected by filtration under reduced pressure, 78% yield 144087-SP-20091119- 1 -162- 201019951 rate. 1 H NMR (400 M), 4.4 (d, 2H), 2.9 (s, 4H), 2.2 (d, 2H), 0.1 (S, 1H); 13 c NMR 172, 154, 74, 28,19, 0. Example 44 gas-breaking acid 4,5·dimethoxy-2-cordylcholine vinegar in carbonic acid double (three gas) S (BTC, triphos) (14 g, 47.2 mo And (4,5-dimethoxy-2-nitrophenyl) decyl alcohol (1 g, 47 mmol) in a stirred solution of 200 ml of THF, added dropwise at (TC) a solution of TEA (65 ml) in _ (150 ml). Upon completion of the addition, the mixture was stirred at room temperature. The solid formed was taken up. The liquid was concentrated to obtain crude carbonic acid 4, 5-methoxy-2-nitrogen vinegar, which is reconciled by benzene 4,5-dimethoxy-2-nitrobenzyl carbonate (10.8 g) was obtained as a yellow solid. 1 H NMR (400 MHz, CDC 13): δ 4 (s, 6H) , 5.7 (s, 2H) 6.9 (s, 1H), 7.7 (s, 1Η). Example 45 Ν·(3-Aminopropyl)-4-(pentyloxy)benzenesulfonamide using hydrazine-(6-aminohexyl)-4-(pentyloxy)benzenesulfonate similarly as in Example 39 Procedure for the preparation of the indoleamine, and replacing the hexane-l,6-diamine with propane-1,3-diamine to prepare the title compound Ν-(3-aminopropyl)-4-(pentyloxy)benzene Sulfonamide. Example 46 Ν-(4.Aminobutyl)-4·(pentyloxy)benzenesulfonamide was used in the same manner as in Example 39: Ν-(6-aminohexyl)-4-(pentyloxy)benzenesulfonate Procedure for the preparation of the indoleamine, and replacing the hexane-1,6-diamine with butane-1,4-diamine to give the title compound Ν-(4-aminobutyl)-4-(pentyloxy) Phenylsulfonamide. 144087-SP-20091119-1 •163·201019951 Example 47 N_(5-Aminopentyl)-4-(pentyloxy)benzenesulfonamide was used as N-(6-aminohexyl) as in Example 39. Procedure for the preparation of -4-(pentyloxy) oxasulfonamide, and replacing the hexane-1,6-diamine with pentane-1,4-diamine to give the title compound N-(5-aminopentane Base)-4-(pentyloxy)benzenesulfonamide. Example 48 Synthesis of Compound (23)

In a solution of vancomycin hydrochloride (5 g) in THF (30 ml) and H20 (20 ml), NaHC03 (1.5 g) was added at room temperature, followed by carbonic acid 4,5- Methoxy-2-nitrobenzyl ester (14 g). The resulting mixture was stirred at room temperature for 2 hours. The solvent was removed under vacuum. The solid formed was separated by chromatography on a silica gel (300 mesh, solvating agent: CH2Cl2 / MeOH = 2/l). Compound (23) (2.6 g) was obtained in 50% yield. Example 49 Synthesis of Compound (24) 144087-SP-20091119-1 • 164-201019951

The compound (24) was prepared by using a procedure similar to that of the compound (23) in Example 48, and replacing the vancomycin hydrochloride with the compound (21).

Example 50 Synthesis of Compound (25)

Add Fmoc-OSu (9-mercaptodecyloxy) to a solution of compound (21) (35.0 g) in 1,4-dioxane (50 ml) and water (50 ml) at room temperature Alkylcarbonyl-0-succinimide (11.0 g) and stirred. After the reaction mixture was stirred at ambient temperature for 2 hr, solvent was evaporated under reduced pressure. The solid which formed was collected by filtration under vacuum and purified by EtOAc EtOAc (EtOAc:EtOAc:EtOAc Example 51 Synthesis of Compound (26) 144087-sp-20091119-1 -165- 201019951

Adding freshly distilled triethylamine (55 mg) to p-pentyloxy chloride at ambient temperature in a solution of compound (25) (1 g) in dry DMF (10 mL) A solution of phenylsulfonate (170 mg) in DMF (1 mL) was stirred. The reaction mixture was stirred for another two hours and then monitored by analytical HPLC. Upon completion, the mixture was poured into ether (100 mL). The precipitated white solid was collected by filtration under reduced pressure to give Compound (26). Example 52 Synthesis of Compound (27)

Compound (26) from Example 51 was dissolved in DMF (9 mL) and then diethylamine (3 eq.) was added at ambient temperature. After stirring at room temperature for 2 hours, the reaction mixture was poured into ether. The solid formed was applied to a preparative HPLC to give Compound (27) (50 mg) as a white powder. The ESIMS m/z is at 1809.3 (90%), 1206.6 (100%), 905.3 (40%). For (: 8711104(:12;^10026 S [M+H]+ ESI-MS m/z calc. 1809.8. Found: 1809.3. 144087-SP-20091119-1 -166- 201019951 Example 53 Compound (28) Synthesis of (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (39), and (40)

144087-SP-20091119-1 • 167-201019951, according to the experimental procedure for the preparation of compound (26) as described in Example 51, gasified benzenesulfonate protected with various phenylsulfonium chloride or an appropriate hydroxyl or amine group, Gasification of p-pentyloxybenzenesulfonate afforded various compounds (26) analogs. These compounds (26) are subjected to a procedure similar to that described for the preparation of compound (27) as described in Example 52 (following the removal protection with respect to a hydroxyl group or an amine-protecting compound) to prepare a compound (28-33) and Compound (36), and Compound (34), Compound (35), Compound (37), Compound (38), Compound (39) and Compound (40) are obtained. Example 54 Synthesis of Compound (41)

CDI (0.7 mL, 1.3 eq.) was slowly added at 0&lt;0&gt;C under EtOAc (EtOAc). After the reaction mixture was stirred at room temperature for 2 hours, a solution of compound (25) (0.55 g) in DMF (7 mL) The resulting mixture was stirred at room temperature for an additional 2 hours. Analytical HPLC monitoring showed completion of the reaction. The reaction mixture was poured into ether. The resulting crude Fmoc- decylamine product (600 mg) was collected by filtration and dissolved in DMF (8 mL). Diethylamine (0.8 mL) was added at room temperature, and the mixture was stirred for 1.5 hr. The mixture was poured into ether. The solid which formed was collected by filtration and applied to preparative HPLC 144087-SP-20091119-1 -168-201019951 to obtain compound (41) (50 mg). ESIMS -MS m/z 1822.1 (100%), [M+CF3COO]· = 1821.7, found 1822.1; +MS m/z at 1709.8 (40%), 1140.0 (100%), 855.4 (60%) [M+H]+1709.7, found: 1709.8. Example 55 Synthesis of Compound (42)

CDI (0.76 mL, 1.4 eq.) was slowly added to a solution of EtOAc (EtOAc). After the reaction mixture was stirred at room temperature for 2 hours, a solution of Compound (25) (0.6 g) The resulting mixture was stirred at room temperature for an additional 2 hours. Analytical HPLC monitoring showed completion of the reaction. The reaction mixture was poured into ether. The resulting crude Fmoc- decylamine product (620 mg) was collected by filtration and dissolved in DMF (8 mL). The mixture was analyzed by analytical HPLC. Upon completion of the reaction, the mixture was diluted with ether (30 mL). The solid which formed was collected by filtration, washed with diethyl ether, dried under vacuo and purified by preparative HPLC to afford 40 mg of compound (42) as white powder. ESIMS -MS m/z at 1835.8 (100%), [M+CF3CO〇r= 1835.7, found: 1835.8; +MS m/z at 1723.7 (100%), 1149.4 (80%), 862.3 (30%) [M+H]+1723.7, found: 1723.7. Example 56 144087-SP-20091119-1 • 169-201019951 Synthesis of Compound (43)

A solution of citric acid (0.8 g) in EtOAc (EtOAc) (EtOAc) The mixture was stirred at room temperature for 2 hours. The resulting mixture was added to a solution of compound (25) (0.62 g) in DMF (7 mL). The mixture was analyzed by analytical HPLC. When the reaction was completed, it was diluted with ether (40 mL). The solid formed was collected by filtration to yield 640 mg of crude Fmocamine compound as white powder. Removal of the Fmoc group by removal of diethylamine results in compound (43). 45 mg of the compound (43) was isolated as a white powder by preparative RP-HPLC. ESIMS -MS m/z at 1849.9 (100%), [M+CF3CO 〇r = 1849.7, found: 1849.9; +MS m/z at 1737.7 (100%), 1158.6 (50%), 869.4 (20%) [M+H]+1737.7, found: 1737.7. Example 57 Synthesis of Compounds 44, 45, 46, 47, 48, 49, 50, 51, 52, 53 and 54 144087-SP-20091119-1 -170- 201019951

The Fmoc-compound (41) analog was obtained by substituting octanoic acid with various carboxylic acids or an appropriate hydroxy group or an amine group-protected carboxylic acid according to the experimental procedure for the preparation of compound (41) as described in Example 54. These Fm〇c_compounds (41) analogs were subjected to a similar removal protection procedure as described in Example 54 (subsequent to removal protection with respect to hydroxyl or amino-protecting compounds) to give compound (44) and compound 144087 -SP-20091119-1 -171. 201019951 Compound (46), and is made into compound (45), compound (47), compound (48), compound (49), compound (50), compound (51), compound ( 52), compound (53) and compound (54). Example 58 Synthesis of Compounds 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68 and 69

144087-SP-20091119-1 -172- 201019951

The Fmoc-compound (41) analogs were obtained by substituting octanoic acid with various carboxylic acids or an appropriate hydroxy group or an amine group to protect the octanoic acid according to the experimental procedure for the preparation of the compound (41) as described in Example 54. These Fm〇c compound (41) analogs were subjected to a similar removal protection procedure as described in Example 54, followed by removal protection with respect to the hydroxyl group or the amine-protecting compound, to give compound (62), compound (63). , the compound (65), the compound (66), and the compound (67), and the compound (55), the compound (56), the compound (57), the compound (58), the compound (59), the compound (60), Compound (61), Compound (68) and Compound (69). Example 59

Synthesis of Compound (70)

a mixture of N-(2-aminoethyl)-4-(pentyloxy)benzene continual amine (29 mg) and vancomycin hydrochloride (145 mg) in acetonitrile (5 ml) and water (5) In a solution of ML), add 37% aqueous formaldehyde (〇2 g) and acetic acid (64 mg) at room temperature. The reaction mixture was stirred at room temperature for an additional 20 hours under reduced pressure 144087-sp-20091119-1 • 173-201019951 The volatile solvent was removed. The solid formed was applied to a preparative hplc to give compound (70) (20 mg) as a white powder. ESIMS-MS m/z 1872.6 (100%), [M+CF3COO]-=1872.7, found: 1872.6; +MS m/z at 1760.4 (40%), 1174.1 (40%), 880.7 (100%) [M+H]+1760.7, found: 1760.4. Example 60 Synthesis of Compound (71)

The compound (71) was prepared by using a procedure similar to that of the compound (25) in Example 50, and substituting the compound (21) with vancomycin hydrochloride. Example 61 Synthesis of Compound (72)

a mixture of N-(2-aminoethyl)-4-(pentyloxy)benzenesulfonamide (151 mg, 0.53 mmol) and compound (71) (1 g, 0.53 mmol) in acetonitrile In a solution of (30 ml) and water (30 ml), add 37% furfural water 144087-SP-20091119-1 -174- 201019951 solution (1.2 g, 14.8 mmol) and acetic acid at room temperature. 640 mg, 10.7 millimoles). The reaction mixture was stirred at room temperature for an additional 20 hours. The volatile solvent was removed under reduced pressure. The formed solid was collected by filtration and washed with EtOAc. The crude product was dissolved in DMF (5 mL). After the addition of diethylamine (22 mg), the reaction mixture was stirred at room temperature for 40 min and then poured into ether (20 ml). The solid formed was applied to preparative HPLC to give compound (72) (25 mg) as a white powder. ESIMS -MS m/z at 1861.1 (100%), [M+CF3C00]-=1860.7, found: 1861.1; +MS m/z at 1748.9 (60%), 1165.8 (40%), 874.9 (100% Under the condition, [M+H]+1748.7, found: 1748.9. Example 62 Synthesis of Compound (73)

Compound (25) (1 g, 0.40 mmol) with N-(2-aminoethyl)-4-(pentyloxy)benzenesulfonamide (120 mg, 0.40 mmol) in acetonitrile (25) Add a 37% aqueous solution of furfural (1 g '12 mmol) to acetic acid (400 mg, 6.7 mmol) at room temperature with a solution of water (25 ml). The reaction mixture was stirred at room temperature for additional 20 hours. The volatile solvent was removed under reduced pressure. The solid formed was collected by filtration and washed with EtOAc. The crude product was dissolved in DMF (5 mL). After the addition of diethylamine (22 mg), the reaction mixture was stirred at room temperature for 40 min and then poured into ether (20 ml). The solid formed 144087-sp.20091119-1 • 175·201019951 was applied to preparative HPLC to give compound (73) (35 mg, 18%) as white powder. ESIMS -MS m/z at 1994.1 (100%), [M+CF3COO]- = 1993.9, found: 1994.1; +MS m/z at 1882.0 (20%), 1254.7 (30%), 941.5 (100%) [M+H]+1881.9, found: 1882.0. Example 63 (74) Synthesis

a solution of the compound (71) (0.95 g) and N-(6-aminohexyl)-4-(pentyloxy)benzenesulfonamide (170 mg) in acetonitrile (40 ml) and water (20 ml) Inside, a 37% aqueous solution of furfural (1 g) and acetic acid (1 ml) were added at room temperature. The reaction mixture was stirred at room temperature for an additional 75 hours. The volatile solvent was removed under reduced pressure. The formed solid was collected by filtration and washed with EtOAc. The crude product was dissolved in DMF (10 mL). After the addition of diethylamine (0.7 mL), the reaction mixture was stirred at room temperature for 1 hour and then poured into ether (35 ml). The solid formed was applied to a preparative HPLC to give Compound (74) (55 mg) as a white powder. ESIMS -MS m/z at 1917.1 (100%), [M+CF3CO〇r = 1916.8, found: 1917.1; +MS m/z at 902.9 (100%), 1203.5 (40%), 1804.9 (40%) Under the condition, [M+H]+1804.8, found: 1804.9. Example 64 Synthesis of Compound (75) 144087-SP-20091119-1 -176- 201019951

a solution of the compound (25) (1 g) and N-(6-aminohexyl)-4-(pentyloxy)benzenesulfonamide (170 mg) in acetonitrile (40 ml) and water (20 ml) Inside, a 37% aqueous formaldehyde solution (1 g) and acetic acid (1 ml) were added at room temperature. The reaction mixture was stirred at room temperature for an additional 75 hours. The volatile solvent was removed under reduced pressure. The formed solid was collected by filtration and washed with EtOAc. The crude product was dissolved in DMF (10 mL). After the addition of diethylamine (1 ml), the mixture was stirred at room temperature for 1 hour and then poured into ether (35 ml). The solid formed was applied to preparative HPLC to give Compound (75) (25 mg) as white powder. ESIMS -MS m/z at 2050.2 (100%), [M+CF3COO] - = 2050.0, found: 2050.2; +MS m/z at 969.5 (100%), 1292.2 (20%), 1938.1 (15% [M+H]+=1938.0, found: 1938.1.实例 Example 65 Synthesis of Compounds 76, 77, 78, 79, 80, 81, 82, 83, 84 and 85

144087-sp-20091119-1 - 177- 201019951

A procedure similar to that prepared for compound (74) in Example 63 was used, and N-(6-aminohexyl)-4-(pentyloxy)benzenesulfonamide was replaced with various appropriate amino-decanamine derivatives. The compound (76-85) was prepared. Example 66 Synthesis of Compounds 86, 87, 88, 89, 90, 91, 92 and 93

144087-SP-20091119-1 - 178 - 201019951

Using a procedure similar to that prepared by the compound (7S) in Example 64, and substituting N-(6-aminohexyl)-4(pentyloxy)benzamine with various appropriate amine-amine derivatives, Compound (86-93). Example 67

Synthesis of Compound (94)

Compound (11) (1 g, 0.649 mmol) was azeotroped three times with toluene and then dissolved in anhydrous pyridine. Gasification of methyl benzene sulfonate (426 mg, 1.95 mmol) in 1 ml of anhydrous pyridine was added dropwise to the solution at 0 ° C, and the mixture was continuously stirred for 2 hours. The reaction mixture was poured into water τ and was taken care of. The solid was purified by flash-phase normal phase column. </ RTI> </ RTI> </ RTI> 144087-sp-20091119-l 179-201019951 Compound (94) was obtained as white solid (500 mg, yield = 50%). LC-MS (ESI): 1620 (M++1). Example 68 Synthesis of Compound (95)

A solution of compound (94) (1 g, 0.581 mmol) and sodium azide (377 mg, 5.81 mmol, 10 eq.) in anhydrous DMF was warmed to 70 &lt;0&gt;C overnight. The reaction mixture was allowed to cool and added to water. The solid was filtered, washed with water and purified with EtOAc EtOAc EtOAc EtOAc EtOAc ). LC-MS (ESI): 1463 (M++l-Boc). Example 69 Synthesis of Compound (96)

To a solution of compound (95) (1 g, 0.639 mmol) in 5 ml of THF containing a few drops of water, n-Bu3P (905 mg, 4.47 mmol) was added. The mixture was heated to reflux overnight, then cooled to room temperature and poured into water. The solid was filtered, washed with water, and purified by flash column reverse phase column (MeCN/ 144087-sp-20091119-1 -180-201019951 H20=l/9~l/3) to obtain compound (96). Yellow solid (100 mg, yield = 10%). LC-MS (ESI): 1537 (M++1). Example 70 Synthesis of Compound (97)

To a solution of the compound (96) (380 mg) in 2 ml of THF and 10 ml of water, (Boc) 20 (1.05 eq.) and TEA (2.0 eq.). The mixture was stirred at room temperature for several hours. Confirmed by HPLC-MS. The solvent was evaporated to give the compound (97). Example 71

Synthesis of Compound (98)

Compound (97) (100 mg) was azeotroped three times with toluene. Then, it was dissolved in 1 ml of anhydrous DMF. Under an argon atmosphere, 1 ml of triethylamine (18.5 mg, 3.0 eq.) in anhydrous DMF was added with an ice bath, followed by the addition of 1 ml of anhydrous 4-ethoxybenzene-1-sulfonate in anhydrous DMF (27). Mg, 2.0 equivalents). The mixture was stirred at room temperature overnight. Confirmed by HPLC-MS. The reaction was quenched by the addition of water 144087-SP-20091119-1 -181 - 201019951 and then filtered. The filter cake was washed three times with water. The crude material was purified by preparative HPLC to give Boc-comp. (98) intermediate. The intermediate was stirred in 2 ml of TFA/DCM (1/1) for about 1 hour with an ice bath. Confirmed by HPLC-MS. The solvent was removed under reduced pressure at 0 °C. The residue is washed with ether and filtered to give the desired compound (98). Example 72 Synthesis of Compounds 99, 100, 101, 102, 103 and 104

A compound (99-103) was prepared by using a procedure similar to the one prepared in the compound (98) of Example 71, and substituting 4-ethoxybenzene-1-sulfonium chloride with various appropriate sulfonium sulfonate derivatives. The compound (104) is prepared without the removal protection of the nitrogen-protected Boc group. Example 73 Synthesis of Compounds 105, 106 and 107

(1ϋ5) (106) (1ΏΖ) 144087-sp-20091119-1 -182- 201019951 In a solution of 200 mg of compound (104) in DMF (2 ml), add 3 molar equivalents of ammonia, guanamine or A sterol solution of guanamine. The solution was stirred at room temperature for 4 hours to obtain a Boc-amino intermediate. The solution of the intermediate in 2 ml of TFA/DCM (1/1) was stirred for about 1 hour with an ice bath. Confirmed by HPLC-MS. The solvent was removed under reduced pressure and (the residue was washed with ether and filtered to give the desired compound (105), (106) and (107). Example 74 Compounds 108, 109, 110 and 111 synthesis

A procedure similar to that prepared by the compound (75) in Example 64 was used, and N-(6-aminohexyl)-4-(pentyloxy)benzenesulfonamide was replaced with various appropriate amines, and the compound (97) was used. The compound (25) was replaced to prepare a nitrogen-protected Boc-compound (108-111). A solution of these Boc intermediates in 2 ml of TFA/DCM (1/1) was stirred for about 1 hour with an ice bath. Confirmed by HPLC-MS. The solvent was removed under reduced pressure at 0 °C. The residue is washed with ether and filtered to give the desired compound (108), (109), (110) and (111). 144087-sp-20091119-1 -183- 201019951 Example 75 Synthesis of Compounds 112, 113 and 114

A procedure similar to that prepared for the compound (75) in Example 64 was used, and the compound (25) was replaced with the compound (97), and the N-(6-aminohexyl) group was also replaced with various appropriate amino groups - continued hydrazino groups. 4-(pentyloxy)benzenesulfonamide was made into a nitrogen-protected Boc-compound (112-114). The solution of these Boc intermediates in 2 ml of TFA/DCM (1/1) was stirred for about 1 hour with an ice bath. Confirmed by HPLC-MS. The solvent was removed under reduced pressure and at 〇 °C. The residue was washed with ether and filtered to give the desired compound (112), (113) and (114). Example 76 Synthesis of Compounds 115, 116, 117, 118, 119, 120, 121, 122, and 123

144087-SP-20091119-1 -184- 201019951

021) U22)

A procedure similar to that prepared by the compound (98) in Example 71 was used, and the compound (97) was replaced with the compound (11), and the vaporized 4-ethoxybenzene was replaced with various appropriate chloro-1-benzenesulfonium derivatives. 1-sulfonium oxime, the compound (117) and the compound (118) are prepared, and the compound (117), the compound (116), the compound (119), the compound (120), the compound (121) and the compound (122) are prepared. . Compound (123) can also be prepared without the removal protection of the nitrogen-protected Boc group. Example 77 Synthesis of Compounds 124, 125 and 126

A solution of 200 mg of the compound (123) in DMF (2 ml) was added with a molar solution of 3 molar equivalents of ammonia, decylamine or dimethylamine. Then, it was stirred at room temperature for 4 hours to obtain a Boc-amino group intermediate. The solution of the intermediate in 2 ml of TFA/DCM (1/1) was stirred for about 1 hour with an ice bath. Confirmed by HPLC-MS. The solvent was removed under reduced pressure at 0 °C. The residue was washed with ether and filtered to give Compounds (124), (125) and (126). Example 78 Synthesis of Compound (127) 144087-sp-20091119-1 -185- 201019951

Addition of compound (1) (14.30 g, 10.95 mmol) to 2-amine adamantane hydrochloride (16.42 mmol, 1.5 eq.) in DMSO (100 mL) at room temperature DIPEA (5.66 g, 4 equivalents) with HATU (4.17 g, 1.0 eq.) and stirred. The reaction was monitored by analytical HPLC. After stirring at room temperature overnight, the reaction mixture was poured into CH2C12 (300 mL) and stirred. The solid formed was collected by suction <RTI ID=0.0></RTI> tojjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj The crude compound (17) (9.38 g) was dissolved in EtOAc (EtOAc) Fmoc-OSu (2.20 g, 6.52 mmol) and NaHC03 (0.55 g, 6.52 mmol) were added to this solution. After stirring at room temperature for 2 hours, the solvent was removed by a rotary evaporator. The residue was purified by flash column chromatography (solvent: MeOH/CH.sub.2Cl.sup.ssssssssssssssssssssssssssssss White powder. ESI-MS m/z, </RTI> </RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; Example 79 Synthesis of Compounds 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138 and 139 144087-SP-20091119-1 -186- 201019951

A procedure similar to that prepared by the compound (75) in Example 64 was used, and the compound (25) was substituted with the compound (127), and various appropriate amines (when there were additional amine groups, the secondary amine group was Fmoc group). The protected derivative is substituted with N-(6-aminohexyl)-4-(pentamethylene)benzenesulfonamide to give the compound (128-139). Example 80 Synthesis of Compound (140) 144087-SP-20091119-1 -187- 201019951

N-(3-Aminopropyl)_4 (penta) was added to a solution of compound (71) (1 g, 0.53 mmol) in CH3CN (30 mL) and H20 (20 mL) Oxyphenyl) benzenesulfonamide (200 mg, 0.67 mmol), aqueous HCHO (37%, 1 g, 23 eq.) and HOAc (200 mL). The reaction was monitored by analytical HPLC coupled with ESI-MS. After stirring at room temperature for 48 hours, the solvent was removed by a rotary evaporator. The resulting white solid was collected by EtOAc (EtOAc) (EtOAcjjjjjjjjj 2218.2, found 2218.8; [M+CF3C02]_= 2331.2, found: 2331.1). The product was treated directly with diethylamine (70 mg, EtOAc, EtOAc) (EtOAc) The reaction mixture was poured into ether. The solid formed was collected by filtration under reduced pressure and washed with ether. The solid was isolated by reverse phase preparative HPLC (C18, <RTI ID=0.0>#</RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; ESI-MS m/z, </RTI> </RTI> <RTI ID=0.0></RTI> </RTI> </RTI> <RTIgt; Example 81 Synthesis of Compound (141) 144087-SP-20091119-1 -188- 201019951

The compound (141) was prepared by using a procedure similar to that of the compound (140) in Example 80, and substituting the compound (71) with the compound (25).

Example 82 Synthesis of Compound (142)

A procedure similar to that prepared for compound (75) in Example 64 was used, and N-(6-aminohexyl)-4-(pentidine) was replaced with N-(2-aminoethyl)octane-1-sulfonamide. Oxy)benzenesulfonamide to give compound (142). Example 83 Synthesis of Compound (143)

144087-SP-20091119-1 -189-201019951 A solution of citric acid (0.8 g) in THF (8 mL). The mixture was stirred at room temperature for 2 hours. The resulting mixture was added to a solution of compound (25) (0.62 g) in DMF (7 mL) at room temperature. The mixture was analyzed by analytical HPLC. Upon completion of the reaction, it was diluted with ether (40 mL). The solid formed was collected by filtration to give 640 mg of Fmoc-carbamide product (143) as a white powder. Example 84 Synthesis of Compound (144)

A procedure similar to that prepared for the compound (75) in Example 64 was used, and the compound (25) was replaced with the compound (143), and N-(6-aminohexyl)-4-(penta) was replaced with aminomethylphosphonic acid. Oxy)benzenesulfonamide to give compound (144). Example 85 Synthesis of Compound (145)

Isocyanate was added dropwise via a syringe at room temperature in a solution of compound (25) (200 mg, 0.1 mmol) in dry DMF 144087-SP-20091119-1 -190-201019951 (1 ml) P-Phenyl sulfonate and stir. The reaction was monitored by analytical HPLC coupled with ESI-MS. After stirring at room temperature overnight, the reaction mixture was poured into ether. The solid formed (about 210 mg) was collected by filtration under reduced pressure, which was confirmed to be a mixture of multiple addition products. The mixture was treated directly with diethylamine (73 mg, 1 mmol, 10 eq.). The reaction mixture was poured into ether. The solid formed was collected by filtration under reduced pressure and washed with ether. The solid was isolated by reverse phase preparative HPLC (C18, EtOAc, EtOAc (EtOAc) ESI-MS m/z, </RTI> </RTI> <RTI ID=0.0></RTI> Example 86 Synthesis of Compound (146)

Add pNZ- in a mixture of vancomycin hydrochloride (100.0 g, 67·3 mmol) and NaHC03 (28.3 g, 336.9 mmol) in THF (700 mL) and water (500 mL) A solution of OSu (56.2 g, 191.2 mmol) in THF (200 mL). The reaction mixture was stirred at room temperature for 2 hours, and the organic layer was separated, and the volatile material was removed under reduced pressure. The solid which formed was collected by suction <RTI ID=0.0></RTI></RTI> to <RTI ID=0.0></RTI> - MS: m/z: calcd for C92H116C12N14027 [M+H]+ 1921.89; found: 1921.5 (33.1%), 1281.1 (28.5%), 961.1 (100%); [M+CF3COO]-2033.5; Value: 2033.6 (100%). Example 87 Synthesis of Compound (147)

Add 2-adamantylamine hydrochloride (24.3 g, 129.5 mmol), DIPEA (46.47 g, in a solution of compound (146) (130 g) from DMSO (1000 mL). 360.2 millimoles) and HATU (54.69 grams, 143.8 millimoles) and stirred at room temperature. The reaction mixture was stirred overnight. Analysis HPLC showed completion of the reaction. The reaction mixture was poured into ice water (2000 mL). A precipitate formed and was collected by filtration. The solid was purified by column chromatography (gum, CH3OH-DCM=l:9-l:5). The collected fractions were concentrated to afford compound (147) (70 g, 58.2% yield from vancomycin hydrochloride) as white powder. ESI-MS: m/z: calcd. </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> ). Example 88 Synthesis of Compound (148) 144087-SP-20091119-1 -192· 201019951

The compound (148) was prepared by replacing vancomycin hydrochloride with a compound (1) prepared in a similar manner as the compound (146) in Example 86. Example 89 Synthesis of Compound (149)

Further, Compound (149) was prepared by substituting Compound (146) using a compound (148) prepared in a compound (147). Example 90 Synthesis of Compound (150)

Included in a solution of 3,4-bis(2-(ethyl((4-methylbenzyloxy))) ethoxy)benzoic acid (0.8 g) in DMF (15 mL) 144087-SP-20091119-1 -193-201019951 DIC (0.5 ml) was slowly added at 40 ° C. After the reaction mixture was stirred at 40 ° C for 3 hours, compound (149) (0.8) was added at this temperature. g) and DMAP (0.2 g). The resulting mixture was stirred overnight at 40 ° C. Analytical HPLC monitoring showed the reaction was completed. The solvent was removed under reduced pressure and ether was added. The crude solid was dissolved in DMF (20 mL) and poured into N-methyl-formoline (0.68 g) and acetic acid (0.28 g) (pH 6.0). In a buffer solution of DMF-H20 (3/2) (20 ml), the resulting two-phase reaction mixture was hydrogenated at 5% Pd/C (0.5 g) at room temperature at 1 atm. The reaction was monitored by analytical HPLC. The reaction mixture was filtered and washed with DMF. The filtrate was concentrated and the residue was solidified with Et20. Purification with C to provide compound (150) (30 mg). ESI-MS: m/z: calc. 171 s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s +CF3COO]-1830.65; found: 1830.5 (100%). Example 91 Synthesis of Compound (151)

A procedure similar to that prepared for compound (150) in Example 90 was used, and 3,5-bis(2-(ethyl((4-nitrobenzyloxy)carbonyl)amino)ethoxy)phenyl) Acid substitution 144087-sp-20091119-1 -194- 201019951 3,4-bis(2-(ethyl((4-nitrobenzyloxy)carbonyl))amino)ethoxy)benzoic acid, made into a compound (151). </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; CF3COO] - 1830.65 ; Found: 1830.5 (100%). Example 92 Synthesis of Compound (152)

In a solution of 3,4-bis(2-(indolyl((4-nitrodecyloxy)))) ethoxy)benzoic acid (3.3 g) in THF (60 mL) DIC (945 mg) was slowly added at room temperature. After the reaction mixture was stirred at room temperature for 2 hours, a solution of Compound (25) (1. The resulting mixture was stirred at 80-90 ° C overnight. The reaction was monitored by analytical HPLC. The reaction mixture was poured into MTBE. The crude product formed was collected by filtration and dissolved in DMF (8 mL). Diethylamine (280 mg) was added at room temperature, and the reaction mixture was stirred for 2 hr. The reaction was monitored by analytical HPLC, the solvent was removed under reduced pressure and ether was added. The solid formed was collected by filtration. The crude solid which had been dissolved in DMF (30 ml) was poured into a buffer containing D-methyl-formoline (2.72 g) and acetic acid (1.12 g) (pH 6.0) DMF-H20 (3/2) In the agent (80 ml). The resulting two-phase reaction mixture was hydrogenated at 5% Pd/C (0.8 g) 144087-SP-20091119-1 -195-201019951 at room temperature at 1 atm. The reaction was monitored by analytical HPLC. The reaction mixture was filtered and washed with DMF. The filtrate was concentrated and the residue was solidified with EtOAc. The solid was collected by filtration and purified by RP-HPLC to afford compound (152) (35 mg). Ugly 51-;\18:11^: Pair (:8911108(:121^2 026 [M+H]+ calculated value 1833.78; measured value: 1733.5 (30%), 917.3 (100%); [M+CF3COO ]- 1945.78; found: 1945.6 (95.1%), 1943.6 (100%). Example 93 Synthesis of Compound (153)

A procedure similar to that prepared for compound (152) in Example 92 was used, and 3,5-bis(2-(methyl((4-nitrobenzyloxy)carbonyl)amino)ethoxy)benzoic acid was used. The compound (153) is produced by substituting 3,4-bis(2-(methyl((4-)benzyloxy)carbonyl)amino)ethoxy)benzoic acid. ESI-MS: Compound (153) m/z: calcd: </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; [M+CF3COO] - 1945.78 ; Found: 1945.7 (100%). Example 94 Synthesis of Compound (154) 144087-SP-20091119-1 - 196 - 201019951

To a solution of compound (96) (100 mg) in 3 mL of DMF, CDI (15.8 mg, 1.5 eq.) and TEA (19.7 mg, 3 eq.). The mixture was stirred at 50 ° C for 3 hours. Confirmed by HPLC-MS. Then, the solvent was removed under reduced pressure. The residue was purified by preparative HPLC to afford compound (154) (68 mg, yield = 68%). LC-MS: 1563.5 (M+1). Example 95 Synthesis of Compounds (155), (156), (157), and (158)

A procedure similar to that prepared for the compound (150) in Example 90 was used, and the compound (149) was replaced with the compound (154), and 3,4-bis(2-(ethyl((4-)-benzyloxy) was used. Carbonyl)amino)ethoxy)benzoic acid, or 3,5-bis(2-(ethyl((4-144087-SP-20091119-1 -197-2010-19951 nitrobenzyloxy) Substituting carbonyl)amino)ethoxy)benzoic acid or other similar benzoic acid, and dissolving the final product in a 1:2 mixture of TFA and di-methane, and treating after 6 hours of stirring to prepare a compound (155), (156), (157) and (158). Example 96 Synthesis of Compounds (159), (160), (161), (162), and (163)

Substituting a protected substituted benzoic acid for 3,4-bis(2-(ethyl((4-nitrobenzyloxy)carbonyl))amino)ethoxy)benzoic acid to give (159), 160), (161), (162) and (163). Example 97 Synthesis of Compounds (164), (165) and (166) 144087-SP-20091119-1 -198- 201019951

A procedure similar to that prepared for compound (152) in Example 92 was used, and 3,4-bis(2-(methyl((4-nitrofluorenyl)oxy)) was substituted with various similarly substituted benzoic acid. Carbonyl)amino)ethoxy)benzoic acid to give compounds (164), (165) and (166). Antibacterial Evaluation The in vitro antibacterial activity was studied in Meuller-Hinton medium by medium dilution method, as recommended by NCCLS. All of the tested strains were clinical isolates that were sensitive or resistant to natural glycopeptides. The MIC value is measured by the medium microdilution procedure recommended by CLSI (the method of the laboratory and the laboratory-like sputum, the method of diluting 细菌 anti-microbial susceptibility test of bacteria growing in a gas-demanding manner; recognized standard - seventh Version, Ammonia Liquid Processor (Multiple Dropper 384, Labsystems, Helsinki, Finland; Biomek 2000 and Multimek 96, Beckman Coulter, Fullerton CA) for continuous-dilution and liquid transfer. The MIC data lines of the representative glycopeptide derivatives prepared and described are extracted in Tables 1 and 2. The MIC value for vancomycin is given for comparison. The abbreviations for the tested organisms are as follows: SA 100 - Jin Suzhen luxury wide. 苈1〇〇 (ATCC 29213); SA 757 - Jin Su Ciyu luxury wide grinding 757 (MRSA); SA 2012 - Jin Suzhen honing honing 2012 (VISA); SE 835 - 4 Dragon 毐 毐 · 835 ; SE 831 - 4犮瘃 求 磨 831 144087-SP-20091119-1 -199- 201019951 (MRSE); EFc 101 - JI 虔 101 (ATCC 29212) ; EFc 848 - # 珠球磨848 (VRE ' VanA ); EFcm800 - Chip I Sulfur Mill 800; EFcm752 - Chip Ball Mill 752 (VRE Van A); SPNE 1195 - Moyi Ball Abrasive Mill ii95 (ATCC 49619); SPY712-叆麇 Chain Ball 712. Biological Data Most of the glycopeptide derivatives in Tables 1 and 2 are extremely effective and resistant Activity of Streptococcus pneumoniae and MRSA (clinically important pathogen). Many derivatives have resistance to vancomycin-resistant bacteria, such as Staphylococcus aureus with moderate resistance to vancomycin and to Van Gogh Phytotoxic enterococci. Table 1 SA SA SA S £ SE EFC EFC EFCM EFCM SPNE SPYO Compound 100 757 2012 835 831 101 848 800 752 1195 712 30 AADBAACABAA 42 AACAAACAAAA 43 ABCAAA c AAA Λ 103 BA c AAADA c BA 102 AABAAADABAA 101 AAAAAACAAAA 99 AABAAABAABA 31 BBDAAAD Λ BA Λ 32 CCDBAADABAA 33 CCEAAADABAA 1J7 AADAAADA c AA 118 DCGCCBDA c Λ A 44 BBDAABGAGAA Vancomycin 1 8 4 2 4 &gt;64 1 &gt;64 0.25 0.5 200- 144087-sp- 20091119-l 201019951 Table 2

SA SA SA SE SE EFC EFC EFCM EFCM SPNE SPYO Compound 100 757 2012 835 831 101 848 800 752 1195 712 106 CCCAABEACCA 63 AADAAAEACAA 62 AADAAAEABAA 46 AADAAADAAAA 65 BADBAAEACAA 67 AACCAAEAC NR A 163 CCCCACGBEBA 166 AACBAAGADAA I6S AA c BAAG Λ DAA 160 CC c BABGA £ BA 162 DCDBACGBFCA 152 AACAAAGAE Λ A 159 BBBBABGAEBA 153 AABAAAGAGAA 164 AACAAAG Λ FAA Vancomycin 2 4 2 2 4 &gt;64 &gt;64 0.25 0.5 MIC value measured in the presence of 0.002% polyphthalate 80 MIC (μg/ml) 0.01 &lt; AS 0.5 0.5 &lt; B^ 1.0 1.0 &lt; C^ 2.0 2.0 &lt;D^ 4.0 4.0 &lt;E^ 8.0 8.0 &lt;F^ 16.0

16.0 &lt; G

Clinical trial of the safety and efficacy of the compound of formula 1 (v) in patients with refractory Clostridium-associated diarrhea. Purpose of the study: The purpose of this study is to determine the safety and efficacy of the glycopeptide compounds proposed herein. Efficacy 'used for the treatment of C. sinensis has associated symptoms of thirst, and reduces the risk of repeated incidents of sputum. Compound (IV) is evaluated in comparison with current standard antibiotic treatments, so all patients will receive active drugs: All study-related caregivers are available, including doctor consultations, physical laboratory tests, and research medications. The total length of participation is approximately 10 weeks. 144087-sp-20091119-l -201 - 201019951 Patients: Qualified patients are 18 years old and older men and women. Criteria: Add standard: at least 18 years old; active moderate to moderate C. difficile associated with cdad; able to tolerate oral medication; not pregnant or breastfeeding; and signed and dated on the consent form . Study Design: This is a randomized, double-blind, live control study of the efficacy, safety, and drug resistance of compounds of the formula (IHV) in patients with C. jejuni associated with ventral disease. Comparison of (IMV) Compounds with Wansuosu for the purpose of clinical trials for the treatment of MRSA (IV) inflammation. The purpose of this study is to determine the glycosaminoglycan compounds proposed in this article, when compared with vancomycin, The efficacy of oxyphenyl phthalocyanine is resistant to golden yellow (four) ball g (MRSA) osteomyelitis. Patients: Qualified patients are 18 years old and older men and women. Criteria: Addition criteria: Cultured WRSA, obtained from bone alone in the operating room or aseptic biopsy procedure. The location of the infection and sampling is in the deep soft group of the bone or adjacent to the bone. Or it is abnormal with the radiation of (4) inflammation, accompanied by a positive blood culture for MRSA; surgical wound incision at the site of infection, as needed 144087-sp-20091119-l -202- 201019951 The patient's department is able to provide a signed consent form that is acceptable for the 12-week exclusion criteria for the perioperative facial treatment: for the formula σ)_(ν) compound or Vancomycin is allergic. Compound 1-(ν) or sex; Staphylococcus aureus resistant to osteomyelitis directly developed from chronic open wound σ; multi-microbial culture (the only exception is if the condensed lineage Exist in culture and clinically evaluated as a contaminant) Staphylococcal patients have a positive pregnancy test at the time of study registration; baseline renal or hepatic insufficiency of study drug administration is excluded; intravenous anti-sounding is administered $ I&amp; The use of active all-injected drugs in the absence of women in Beijing is over 3 months; and for infections other than osteomyelitis, antibiotics are expected to last for more than a day. © Study Design: This is a randomized, open-label, active control, efficacy trial comparing vancomycin with compounds of formula (I)-(V) for the treatment of MRSA osteomyelitis. In the case of a serious infection caused by vancomycin-resistant Enterococcus (VRE), the clinical trial of the compound of the formula (IMV) was evaluated. The purpose of this study was to select the cause of VR £ The safety and efficacy of the compounds of formula (I)_(V) are determined in the treatment of severe infections. Patients: Qualified patients are 18 years old and older men and women. Standard: Add standard: 144087-SP-20091119-1 •203- 201019951 One of the following antibiotic-resistant bacteria: resistance to vancomycin-resistant Enterococcus faecalis, resistant to vancomycin Enterococcus faecalis, or as part of a multi-microbial infection; with severe infections (eg, bacteremia [unless due to excluded infections], concurrent intra-abdominal infections, complicated skin and skin structure infections or pneumonia) Confirmation of diagnosis requires intravenous αν) antibiotic therapy. Exclusion criteria: Eight patients with any coexisting symptoms or taking any coexisting drug may exclude the assessment of the response according to the opinion of the researcher, or make the intended treatment process or follow-up assessment unlikely to be completed, or substantially increase Patients are at risk associated with participating in this study. The expected length of antibiotic therapy is less than 7 days. Study Design: This is a randomized, double-blind, safe, and efficacy study of compounds of formula (Ι)-(ν) in the treatment of severe infections caused by yjyg. Although the specific embodiments have been described in considerable detail for the purpose of clarity of understanding, it should be understood that in some embodiments, certain changes and modifications are within the scope of the appended claims . The present invention is to be considered as illustrative and not limiting, and the aspects described herein are not limited to the details disclosed herein, but in some embodiments, The scope of the request and the equivalents are corrected. 144087-SP-20091119-1 -204-

Claims (1)

201019951 VII. Patent application scope: Wherein ra is selected from the group consisting of a) hydrogen, 144087-sp-20091119-2 201019951 b) sulfhydryl, c) C2 _Ci 2 - alkyl, and the 112 and 12 are each independently selected from the group consisting of a) hydrogen, b) Ci-Ci 2_alkyl, C) Ci-Ci 2-alkyl substituted by one or more substituents selected from the group consisting of (8) i, (b) hydroxyl, (c) Ci-Ci2_alkoxy, (6)q-cv alkoxy-CVC3-alkoxy, (e) amine group, (f) (ν&lt;:12-alkylamino group, (g) q-Cu- Dialkylamino, (8) alkenyl, (1) alkynyl, G) Ci -C^ 2 - thioalkyloxy' d) Ci-Cu-alkyl substituted by aryl, e) substituted by substituted aryl (^-(:12-alkyl, f) substituted by a heteroaryl group (^-(:12-alkyl, g) substituted by a substituted heteroaryl group of q-Cu-alkyl, h) ring Alkyl, i) cyclodecyl, j) heterocycloalkyl, 144087-sp-20091119-2 -2- 201019951 • The reference or W and the atoms to which they are attached are used to form substituted heteroaryl or 3-K) A heterocycloalkyl ring, which optionally contains one or two heterofunctional groups, is selected from the group consisting of: 〇...nh, - -C6 -alkyl)-, -N(aryl)·, _N(aryl%alkyl)_, -N(substituted-aryl-C! _C6_alkyl)_, _N(heterofang Base, _, heteroaryl-CV alkyl-)-, -N (substituted-heteroaryl), S- and S(〇)n_ 'where n is 1 or 2' and the 3_ι〇 The heterocycloalkyl ring system is optionally substituted by one or more substituents independently selected from the group consisting of the following constituents (8), (b) via, (c) Q-C3-hyun&gt;oxy , (6) Q -C3 - alkoxy-C3 - alkoxy, (6) keto, (0 Cl -C3 -alkyl, (g) Cl -C3 - dentate, (h) q-CV alkoxy-q -CV 炫, • and k) c(=o)r7, 1) C(=O)CHR8NR9R10, wherein r8, r9&r10 are each independently selected from the group consisting of hydrogen, lower alkyl, Substituted lower alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, 144087-SP-20091119-2 201019951 or 'form 3-1 取代 substituents take R·9 and Ri 〇 and their attached atoms together employ a heterocycloalkyl ring, which is optionally one or more generations, and the substituents are independently selected from the group consisting of (8) halogens, groups (b) (c) C! -C3 - alkoxy, (6) Q-cv alkoxy_Ci_c3_alkoxy, (e) keto, (f) Q-C3 -alkyl, (g) C! -C3 -halogen Alkyl, (h) q-Cy alkoxy_Ci_C3_alkyl; R7 is selected from the group consisting of a) hydrogen, b) C!-Ci 2 · entertainment * base, C) is - or more a substituent-substituted Ci_Ci2 alkyl group, the substituent being selected from the group consisting of (8) halogen, (9) hydroxyl, (c) &lt;VC12-alkoxy, (6) Ci-CV alkoxy_Ci_c3_oxy, (6) amine, (f) (Vc12•alkylamino, (g) cvc12-dialkylamino, 144087-sp-20091119-2 201019951 (8) alkenyl, (i) alkynyl, 1CVCu-thioalkoxy, d) aryl a substituted q-Cu-alkyl group, e) a q 2-alkyl group substituted with a substituted aryl group, f) a heteroaryl substituted alkyl group, g) a q-Cu substituted with a substituted heteroaryl group -alkyl, h) cycloalkyl, i) cycloaliphatic, j) heterocycloalkyl, k) Ci-Ci 2 - acrylamine, l) amine, Π 1) amine-cycloalkyl; a group selected from the group consisting of (1) hydrogen, (2) gas; Y system selected from the group consisting of (1) oxygen, (2) NRi; T system selected from the group consisting of 1) -so2RB, (2)-CORB, (3) -C0NHS02RB; R is selected from the group consisting of 144087-sp-20091119-2 201019951 (1) hydrogen, (2) cycloalkyl, (3) cycloalkenyl, (4) C! -C! 2 -alkyl group, (3) Ci-Cu-alkyl substituted by one or more substituents selected from the group consisting of: (8) 4, (b) merid, (c) CVC12 - alkoxy, ® (9) CVC3 · alkoxy-Cl &lt; v alkoxy, (6) -COOR5 'where r5 is hydrogen or lower alkyl, (f) -C(0)NR5R6 'where R6 is hydrogen or low carbon Alkyl, (g) amine, (h) -NR5R6, or Rs is used together with Re and the atoms to which they are attached to form a 3-1 membered heterocycloalkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of Halogen, (ii) hydroxy' (iii) (VC3-alkoxy, (iv) (VQ-alkoxy-Cl-C3-morphyloxy, (V) network, (vi) Cl-Cl 2 - Pyridyl, 144087-sp-20091119-2 -6- 201019951 (vii) Ci-Ci 2 _ alkyl, and (viii) CVC3-alkoxy-q-Cu-alkyl, (1) aryl, 1 substituted Aryl, (k)heteroaryl, (1) substituted heteroaryl, (m) thiol, (n) Ci-Ci 2 - thioalkyloxy, (6) ¢: (=0)01^ !, Center i is hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, (7) ChC^NRuRu, wherein Ru is as defined above, and Is hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, 或 or heart! attached to R! 2 and to them The atoms together form a 3-bonded heterocyclic ring - 9 base ring, which is taken as the case - or multiple Substituent substitution, which is independently selected from the group consisting of (8) _ prime, (b) thiol, (c) alkoxy, (d) &lt;:1&lt;:3-alkoxy&lt;:1&lt;;: 3-alkoxy, (6) keto, 144087-sp-20091119-2 201019951 (f) ei'Cl2-alkyl, (g) substituted lower alkyl, (8) Cl 2 halo, (i) Amino group, (j) alkylamino group, (k) dialkylamino group and 1 alkoxy _Ci_Ci2 alkyl group, or R and its linked oxygen atom together are halogen; R3 is selected from the group consisting of (1) OH , (2) 1-adamantanamine, (3) 2-adamantanyl, (4) 3-amino-1-adamantanyl, (5) 1-amino-3-adamantanyl, (6) 3-lower Amino-1-adamantanylamino, (7) 1-low-alkylamino-3-adamantanylamino, (8) Amino (9) NRi 3Ri4 ' wherein Ri3 and Ri4 are each independently selected from the group consisting of Group: hydrogen, low carbon alkyl, substituted lower alkyl, cycloalkyl, substituted cyclononyl, amine low carbon alkyl Unsubstituted or substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl Arylaryl, alkoxy, aryloxy, -8* 144087-SP-20091119-2 201019951 Substituted alkoxy and substituted aryloxy or substituted with r14 and the atoms to which they are attached - Forming 3 cases of a heterocyclic compound ring which is optionally substituted with one or more substituents, the substituents are independently selected from the group consisting of (8) dentate, (b) hydroxyl group, (c) CVC3-alkoxy , (d) c! -c3 - alkoxy-Cl _c3 • alkoxy, (6) keto, (7)-Ci 2 -institution, (g) substituted lower alkyl, (h) Ci -Ci 2 ώ alkyl, (1) amine, 1 alkylamino, (k) dialkylamino and (l) Ci-Cg-decyloxy-Ci-Cu·• yard base; R4 is selected from the group consisting of the following groups (1) CI^NH-CHRwKCHA-NHSOzRb, wherein the melon is 1 to 6, and Ri 5 is hydrazine or a low carbon alkyl group, (2) CH2NH-CHR15-(CH2)p-CONHS02RB, wherein ρ is 〇 to 6, and R15 is Η or lower alkyl, (3) CH2NH-CHR15-(CH2)p-COOH, where ρ is 〇 to 6, and r15 144〇87-sp-2(X)91119-2 -9- 201019951 is Η or low carbon Alkyl, (4) CH2NRD-CHR15-(CH2)q-NRES02RB, where (} is 2 to 4 and Ri5 is ruthenium or low carbon The base, rd and re together represent (3) Η, (6) CH2NHCH2P03H2, (7) an amine lower alkyl group in which the amine moiety of the amine lower alkyl group is further unsubstituted or substituted alkyl 'Alkenyl, cycloalkyl, cycloalkenyl, arylaryl, alkoxy, aryloxy, substituted alkoxy and substituted aryloxy; RB is selected from the group consisting of a An aryl group, b) Q-Cu-alkyl group, c) a 2-alkyl group substituted by one or more substituents selected from the group consisting of (a) _, (9) hydroxy, (6) Ci A2- Alkoxy, (9) alkoxy_Cl_C3_alkoxy, (6) amine, 1Ci-Ci 2-alkylamino, (8) ci_C12-dialkylamino, (8) alkenyl, 1 alkynyl, 1Ci-C12-thioalkyl Oxyl, 144087-SP-20091119-2 -10- 201019951 d) q-Cn-alkyl substituted by aryl, e) substituted iQ-Cu-alkyl by substituted aryl, f) heteroaryl Substituted (^-(:12-alkyl, g) Ci-Cu-alkyl substituted by substituted heteroaryl, h) cycloalkyl, i) heteroaryl, j) heterocycloalkyl, k) an aryl group substituted by one or more substituents selected from the group consisting of (8) halogen, (b) hydroxyl, (c) CVCu-alkoxy, (6) CVCV alkoxy-(VCV alkoxy) , (6) Amino, (f) Amino-CVCV alkoxy (g) Cl -Cl 2 -Acetylamine ' (h) Ci -Ci 2 -Acetyl-Ci -Cg -Hyun"milk-based (i Ci-Ci 2_diamined amine' (j) Ci -Ci 2 _ II compound amine-Ci -Cg - calcined base, (k) alkenyl group, (l) alkynyl group, (m) CVC12-sulfur Alkenyloxy, (8)Cl -Cl 2 -alkyl, (6)q-Cu-substituted alkyl, 144087-sp-20091119-2 -11 - 201019951 (p) Qc^-alkoxy-morpholinyl, (q a qc^-alkoxy-q-Cu-dialkoxyamino group, (r) q-Cu-alkoxy-nhS〇2Ci_C6 fluorenyl, (8) q-Cu-alkoxy-NHCOq-CV alkyl; a heteroaryl group substituted by one or more substituents, a substituent selected from the group consisting of (8) halogen, (b) hydroxyl group, (c) CVCu-alkoxy group, (d) QQ-alkoxy-q- Cr alkoxy, (e) amine group, (g) C1_C12-alkylamino group, (h) C1-CU-alkylamino group_Cl_c6-alkoxy group, (1) C1_C12-dialkylamino group, 1C!-Ci 2 - Dialkylamine _Ci _Q alkoxy, (k) Alkenyl, 1 alkynyl, (m) Cl-Ci2_thiooxooxy, (8) alkyl, (9) C1 to C12-substituted alkyl; Rc each independently selected from the group consisting of a) hydrogen, b) C1-C12-Alkyl, 144087-sp-20091119-2 201019951 c) A group consisting of one or more substituents, a C!-Ci 2 -histyl substituent, selected from the group consisting of the following: (a) _ , (b) hydroxy, (c) Ci_C12-alkoxy, (6) cVca oxyoxy, (6) amine, 1CVC12-alkylamino, (g) Ci-Ci2-dialkylamino, (h) alkenyl, (i) alkynyl, 1q-Cu-thioalkoxy, d) Ci_Ci2_alkan substituted by aryl a group, e) a substituted aryl group substituted with a hexa-alkyl group, f) a heteroaryl substituted 〇^-(:12-alkyl, g) substituted by a substituted heteroaryl Ci_Ci2_alkane Base, h) cycloalkyl, i) cycloalkenyl, j) heterocycloalkyl, k) C(=0)R7, l) ChCOCHRsNRgRi 0, wherein R8, r9 and R1 are each independently selected from the group consisting of Group: hydrogen, lower carbonyl, substituted low carbon alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, 144087-sp-20091119-2 •13- 201019951 or R々R10 and the atoms to which they are attached are substituted by forming a (four) member heterocyclic ring, which is substituted by a money or a plurality of substituents, and the substituents are independently selected from the group consisting of (8) i, (b) Base, (6) Ci-C3 - alkoxy, (6) Cn-CV alkoxy-Ci-Cy alkoxy, (e) keto, (f) C! · 〇3 - alkyl, (g) C! - C3 An alkyl group, (h) q-C3-alkoxy-C3-alkyl; or pharmaceutically acceptable Salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof. 2. The compound of claim 1, wherein the compound has the formula I Or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary salt, stereoisomer, tautomer or prodrug thereof. 3. The compound of claim 1, wherein the compound has the formula π 144087-sp-20091219-2 14- 201019951 Or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt stereoisomer, tautomer or prodrug thereof. 4. The compound of claim 1, wherein the compound has the formula CHjOH HO ,RC \ NH HaC^^O^Hd10· 0Η3 〇 Cl Or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof. 5. The compound of claim 1 wherein the compound has the formula IV Or a pharmaceutically acceptable salt, ester, solvate, alkylated quaternary ammonium salt, stereoisomer, tautomer or prodrug thereof. 144087-sp-20091119-2 -15- 201019951 Or - pharmaceutically acceptable salts, g, solvates, alkylated quaternary salts, stereoisomers 'tautomers or prodrugs. 7. The compound of claim 2, wherein Ra is hydrogen or methyl and R4 is nitrogen. 8. The compound of claim 3, wherein Ra is hydrogen or sulfhydryl, and &amp; is nitrogen. 9. The compound of claim 4, wherein, is hydrogen or sulfhydryl, and R4 is hydrogen. 10. The compound of claim 5, wherein hydrazine is hydrogen or gas and &amp; is hydrogen. 11. The compound of claim 6, wherein Ra is hydrogen or sulfhydryl, and &amp; is hydrogen. 12. A compound according to the formula i, wherein τ is hydrogen, and R4 is Ch2Nh chRi 5_(cH2)m-NHs〇2RB, wherein to 6, and 11 is a lower alkyl group. 13. The compound of β, wherein i is hydrogen or a sulfhydryl group, and τ is _s〇2Rb. 14. A compound according to claim i, wherein, is hydrogen or methyl, and τ is _c〇RB. 15. A compound according to claim 4, wherein the compound is hydrogen or sulfhydryl, and τ is -conhso2rb 〇16. The compound of claim 1, wherein each of the R3 groups is selected from the group consisting of (1) OH, (2) 1-adamantane Amino, (3) 2-adamantanylamino, 144087-sp-2009lll9-2 -16- 201019951 (4) 3-amino-1-adamantanylamino, (3) 1-amino-3-adamantanylamino, (6)3- a lower alkylamino-1-adamantanylamino group, (7) 1-lower alkylamino-3-adamantanylamino, (8) an amine group (9) NR1SR14, wherein the ruler and the Rh group are independently selected from the following components Group: hydrogen, lower alkyl, substituted lower alkyl, cycloalkyl, substituted cycloalkyl, amino lower alkyl, wherein the amine moiety of the amine lower alkyl Further substituted by unsubstituted or substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, arylaryl, alkoxy, aryloxy, substituted alkoxy and substituted aryloxy Or the core 3 together with &amp; 4 and the atoms to which they are attached form a 3_1 membered heterocycloalkyl ring which is optionally substituted with one or more substituents independently selected from the group consisting of Group 10 (8) ii, (b) thiol, (6) (VC3-alkoxy, (d) C! -C3 - alkoxy-C! -C3 - alkoxy, (6) keto, (0 C}-Ci 2—alkyl, (g) substituted lower alkyl, (h) mercapto Ci-Ci 2 -alkyl, (i) amine, 144087-sp-20091119-2 •17- 201019951 (i) alkane Amino group, (k) dialkylamino group and (l) G-C3-Hyun-oxy-C 2 -alkyl group. 17. The compound of claim 1, wherein each of the Rb groups is selected from the group consisting of a) aryl, b) Ci~C12_alkyl, c) CfCu-andyl substituted with one or more substituents selected from the group consisting of (8) halogen, (b) hydroxyl, (c) C--C12-alkoxy, (d) q-Cs-alkoxy-Cl-c3-alkoxy, (6) amine, (1) Cj-Cu-alkylamino, (g) C1-C12-dialkylamine , (9) alkenyl, 1 alkynyl, 1Ci-Ci2-thioalkoxy, Ci_Ci2_alkyl substituted by aryl, e) ^-heart alkyl substituted by substituted aryl, f) Substituting iCi_Ci2_alkyl by a heteroaryl group, g) Ci_Ci2 alkyl substituted by a substituted heteroaryl group, h) cycloalkyl, 144087-sp-20091119-2 18-201019951 i) Heteroaryl, j) heterocycloalkyl, k) an aryl group substituted by one or more substituents selected from the group consisting of (8) alizarin, (b) mercapto, (6) Ci-Ci 2 _ oxygenated base' (d) C! -C6-Alkoxy-Ci-C6-alkoxy, (6) Amine, (f) Amino-Ci-CV alkoxy, (g) Cl-Cl 2 _ aristyl' h) Q 2 -Acetyl-C-C6-alkoxy, (1) Cl-Cl 2-diamine, 1q-Cu-dialkylamino-q-cv alkoxy, (k) alkenyl, (l) alkynyl, (m) Ci-Ci2_thiomorphoxy, (8) Cl-Cl 2 -alkyl, (9) Ci-Cu-substituted alkyl, (p) Q -C^ 2 - alkoxy-?福普林基, (q) CVCu-alkoxy-q-Cu-dialkoxyamino, (r) CVCu-alkoxy-NHSC^CVQ-alkyl, (s) CVC12-alkoxy- NHCOq-Q-alkyl; l) Heteroaryl substituted by one or more substituents selected from the group consisting of 144087-SP-20091119-2 • 19- 201019951 Groups (8) _, (b) Hydroxy, (6) Ci-Cu-alkoxy, (d) q-cv alkoxy-CVCV alkoxy, (6) amine, 1 amino-CVCV alkoxy, (g) q-Cu-alkylamine, ( h) Ci-C12-alkylamino-CrCV alkoxy, 1 diamined amine, 1Ci-Ci2_ II-amino-Ci-Cg-alkoxy, (9)alkenyl, 1 alkynyl, (m) C -Ci 2 -thiooxooxy, (8) CpCu-alkyl, (〇) c--q 2 - substituted alkyl. 18. The compound of claim 7, wherein the R groups are each selected from the group consisting of T columns (1) hydrogen, (2) cycloalkyl, (3) cycloalkenyl, (4) (VC12-croplex, (5)- Or a plurality of substituents substituted by C]-C12-alkyl, the substituent is selected from the group consisting of (a) _, 144087-sp-20091119-2 201019951 (b) thiol, (c) q-Cu - alkoxy, (d) Ci -C: 3 -alkoxy-C! -C3 -alkoxy, (e) -COOR5 'wherein R5 is hydrogen or lower alkyl, (f) -C(0 NR5R6 'the center is hydrogen or lower alkyl, (g) amine group, (h) -NRjI^ &gt; or ❹ R5 and R6 together with the atoms to which they are attached, forming a 3-10 member heterocyclic ring a base ring, which is optionally substituted with one or more substituents, the substituents being independently selected from the group consisting of (1) halogen, (ii) hydroxyl, (iii) C! -C3 - alkoxy, (lv) q -C3 -alkoxy c3 -alkylindolyl, φ (v) keto, (vi) Ci-Ci 2-homogeneous, (νϋ) (ν(:12_ alkyl, and (10) bis-alkoxy- Cl&lt;::12-alkyl, (1) aryl, 1 substituted aryl, (k)heteroaryl, 1 substituted heteroaryl, 144087-SP-20091119-2 -21- 201019951 (m) thiol, (8) Q 2-thioalkoxy, (6)C(-0)0Rn 'where R&quot; is hydrogen, lower alkyl, substituted lower alkyl, aryl' substituted An aryl group, a heteroaryl group or a substituted heteroaryl group, (7)c(=o)nrur12 ' wherein &amp; is hydrogen, a low carbon alkyl group, a substituted lower fluoroalkyl group, a substituted aryl group, a hetero An aryl or substituted heteroaryl group, or a ruthenium, together with the atoms to which they are attached, form a heterocycloalkane ring, which is optionally substituted with one or more substituents, independently selected from the substituents From the following group (8) _ prime, (b) thiol, - (c) q-Cr alkoxy, (d) Q -C3 - leucoyloxy-C3 - alkoxy, (6) keto, 1q -Cu-alkyl, (g) substituted lower alkyl, (h) Ci-Ci 2 haloalkyl '1 amine, 1 alkylamino, (k) diamined amine and (l) C! -C3 - alkoxy-Cl-C! 2 -alkyl, 144087-SP-20091119-2 -22· 201019951 or R and its attached oxygen atom together as _ 素. 19 · Requests 9 to 10 and The compounds of any of 12 to 17 are independently selected from the group consisting of a) hydrogen b) Ci-Ci 2- burn-yl, C) by one or more substituents of Cl_Ci2_ alkyl, the group of columns Wherein each substituent of the Rc group is selected from the group consisting of (8) halogen, (9) hydroxyl, (6) Cl-Cl2-olyloxy, (d) CVCV alkoxyoxy, (6) amine, (0C-C12-anisamine, (g) CrC12-dialkylamino, (h) aryl, (1) alkynyl, (j) (Vc12-thioalkoxy, Φ substituted by aryl, Cl_c12-alkyl, e) substituted Substituted (^-(:12-alkyl, f) substituted by heteroaryl C]-C! 2-alkyl, g) q-Cu-alkyl substituted by substituted heteroaryl, h Cycloalkyl, i) cycloalkenyl, 144087-sp-20091119-2 -23- 201019951 j) heterocycloalkyl, k) C(=〇)R7, D C(tetra)CHR8NR9Rl0 'where R8, % and Ri〇 are independent A group selected from the group consisting of t, a lower carbon group, a substituted lower carbon base, an aryl group, a substituted aryl group, a heteroaryl group or a substituted heteroaryl group, or a ruler 9 and Ri. And the atoms to which they are attached are used to form a 3 (1) heterocycloalkyl ring which is optionally substituted by one or more substituents independently selected from the group consisting of (8) i, (9) (c) q-CV alkoxy, (6) q-Cr alkoxy-q-Cr alkoxy, (6) keto, 1q-Cr alkyl, (g) Q-C3 halo, (h) C1-C3 - alkoxy-q-Cs-alkyl. 20. The compound of claim 8, wherein the Ri(R) is independently selected from the group consisting of a) hydrogen, b) Ci-C12-leuco, c) Ci_Ci2_alkyl substituted by one or more substituents , Substituents from the following group (8) Nansu, 144087-sp-2009lll9-2 -24· 201019951 (b) Meridian, (c) q-Cu-alkoxy, (d) q-C3-院Oxyoxy, (6) amine, (7) Cl-Ci2-alkylamino, (g) (ν〇: 12-dialkylamino, (h) alkenyl, (0 alkynyl, 1q-Cu-thioalkoxy, Φ substituted by aryl (^-(:12-alkyl, e) substituted by substituted aryl 〇1 must be 2 alkyl, f) substituted by heteroaryl iCi-Cu-alkyl, g) alkyl substituted by substituted heteroaryl, h) cycloalkyl, &amp; i) cycloalkenyl, j) heterocycloalkyl, or heart and ruler 2 and their The attached atom - used to form a substituted heteroaryl or a 3-1 member heterocyclic alkyl ring, optionally containing one or two heterofunctional groups selected from the group consisting of: 〇 _, 视, ΝΑ%·alkyl)-, -N(aryl), _N(aryl_Ci_C6_morphyl_)·, _n(substituted aryl)-C6-alkyl-)-, -N (heteroaryl)..._N(heteroaryl&amp;alkyl-)-, -N(substituted-heteroaryl-Cl alkyl)_, _s_ and s(〇)n, where η is 1 or 2, and the M0 member heterocycloalkyl ring system is optionally substituted by one or more 144087-sp-20091119-2 -25-201019951 substituents, the substituents are independently selected from the group consisting of the following groups (8), (b) Hydroxy, (c) Q-Cr alkoxy, (d) q-cv alkoxy-q-CV alkoxy, (6) keto, (f) C! -C3 - alkyl, (g) (VC3 halogen Alkyl, (h) Q-C3-alkoxy-CVC3-alkyl, k) C(=〇)R7, l) C(=O)CHR8NR9R10 'where r8, uldent 9 and Ri 〇 are independently selected from the following groups: Hydrogen, lower alkyl, substituted lower alkyl, substituted aryl on aryl, heteroaryl or substituted heteroaryl, or substituted with 'substituting 3-10 member heterocycles , replacing % with R10 and the atoms to which they are attached - a cycloalkyl ring which is optionally selected from the group consisting of (8) i, (b) hydroxyl, (c) C - C3 - Alkoxy, (6)q-cv alkoxy_Ci&lt;:3_alkoxy, (6) network, (f) Cl-C3 -yard, 144087-sp-20091119-2 -26- 201019951 (g) CVQ halogen Alkyl, Ql) Cl -C3 -Oxygen!-Cl-C3 -yard group, wherein R7 is selected from the group consisting of a) hydrogen, b) Ci-Ci 2_alkyl group c) a plurality of substituent-substituted q-Cu-alkyl groups, the substituent being selected from the group consisting of the following constituents (8) halogen, (b) hydroxy, (c) CVCu-alkoxy, (d) Cl-C3-alkoxy-Cl-C3-homo-oxy[(6)amino, (f) q-Cu-alkylamino, ( g) Cl-Cl 2 _diamine, (8) alkenyl, (i) alkynyl, 1q-Cu-thioalkoxy, d) CVCu-alkyl substituted by aryl, e) substituted An aryl-substituted (^-(:12-alkyl, Ό substituted by a heteroaryl group (^&lt;12-alkyl, g) substituted by a substituted heteroaryl group of q-Cu-alkyl, h) Cycloalkyl, i) cycloalkenyl, j) heterocycloalkyl, 144087-sp-20091119-2 -27- 201019951 k) 〇ν(:12-alkylamino, l) amine, m) amine- Ring Hyun* base. 21. A compound having a chemical formula selected from the group consisting of the following structural formula 144087-sp-20091119-2 28 - 201019951 OH OH 144087-sp-20091119-2 -29- 201019951 Γη〇η Γη 〇h Nh2 .OH OH (4) Knowledge HN^O Η I 1 -t-OH OH HN^O m) (48) 144087-sp-20091119-2 -30- 201019951 144087-sp-20091119-2 -31 201019951 144087-sp-20091119-2 -32- 201019951 144087-sp-20091119-2 33· 201019951 22. A pharmaceutical composition, 1 comprising a therapeutically effective amount of a composition as claimed, along with a pharmaceutically acceptable excipient or excipient. 23. A method of treating a mammal in need of such treatment, comprising administering to the dairy animal an antibacterial effective amount of a compound, such as a compound of claim 1, pharmaceutically acceptable Carrier or sputum agent. 24. The preparation of a compound of formula I-V * a , 々, which includes: modification of a compound from the group consisting of formulas i, a ϋ and V, 144087-SP-20091119-2 **34. 201019951 Wherein RA is hydrogen or methyl, hydrazine is hydrogen or hydrogen, R3 is OH or alkoxy, 2-adamantanyl or lower alkylamino, as defined herein, R4 is hydrogen or protected CH2NHCH2P〇3H2 or Boc - an amino lower alkyl group, as defined herein, by a technique selected from the group consisting of: (8) 9-fluorenylcarbonyl (Fmoc) or a third-butoxycarbonyl (Boc) or its other Suitable nitrogen protecting group, protecting the amine group, (9) making the third amino acid aspartate one of the guanamine groups, rb S〇2C1 'RBCOOH, using a coupling reagent' or RBS02-NC0 group, in a base such as triethylamine And the presence of a deuteration, (6) removal of the protecting group of the amine group, wherein the Boc protecting group is removed with a mild acid such as trifluoroacetic acid, and the Fmoc group is removed by a test such as diethylamine, (d) Rs is an alkoxy group, and the carboxylic acid derivative is obtained by a mild test or acid hydrolysis to remove the oxygenated 144087-SP-20091119-2 -35»201019951 base, and (6) the azide functional group is reduced to an amine, 1 An amino group-substituted alcohol or a group of amino acid groups on the amine group of the compound is substituted with an amine group on the sugar group to have a structure RJ (wherein J is a halogen) Alkylation of an alkyl halide of R1_J (wherein J is a halogen), R2-J (wherein J is a halogen) or RC-J (wherein J is a halogen), (g) a monosaccharide of a monosaccharide or The amine substituent on the amino group-substituted sugar moiety of the fourth amino acid of the compound is deuterated by a thiol group having the structure c(=〇)R7 ,, (8) the monosaccharide or the compound of the monosaccharide The amine substituent on the amino group-substituted sugar moiety of the 4th amino acid is brewed by a brewing group having the structure C(=0)CHR8 NR9 R! Q, 1 the fourth amine group of the compound The amino group of the acid group is substituted with an amine group on the sugar moiety, reacted with an acid or a ketone, followed by reductive amination of the formed imine, 1 will be an acid moiety on the macrocyclic ring of the compound. The group is converted by a substituted decylamine as defined by R3, (k) reacting with a phosgene of a monosaccharide moiety of the fourth amino acid of the compound with a phosgene adjacent to the thiol group ( l) For the 7th amino acid of the compound, where r4 is hydrogen, and ]^112-CHR! 5 -(CH2)m-NHS02 Rb ^ NHRD-CHRj 5 -(CH2 )q -NRE S02 RB or NH2 - CHR 〖5 -(CH2) p-CONHSO2 Rb 'Mannich 144087-SP-20091119-2 •36· 201019951 in acetonitrile and water or other suitable organic solvent in the presence of aqueous solution of A road, (m) (a), (b) and a combination of c), (8) a combination of (a), (b), (c) and (d), (6) a combination of (8), (b), (6), 1 and (c), (p) (8), (b), a combination of f) and (c), a combination of (6) (8), (8), (g) and (c), a combination of (r) (8), (b), (h) and (c), (8) (8), (b), (i) Combination of (c), (1) (8), (b), (e) and (c), (8) (8), (b), (6), (d) and (c), (v) (a), (8) , (6), 1, (6) and (c), (w) a combination of (8), (b), (d), (e) and (c), (8) (8), (b), (d), (j), a combination of (e), (f) and (c), (y) a combination of (8), (9), (d), 1, (e), (g) and (c), (2) (8), (b), (6), 1 , (6), (h), and (6), (aa) (8), (b), (d), 1, (e), (1), and (c), (bb) (8), (9), (6), (e) , (f) and (c), (cc)(4), (9), (6), (e) a combination of (g) and (c), (dd) a combination of (8), (b), (6), (6), (h) and (c), (ee)(8), (9), (6), (e), (i) and a combination of (c), (ff) a combination of (8), (b), (k) and (c), a combination of (gg) (8), (8), (k), (6), 1 and (c), (hh) (8) , (9), (6), (k) and (c), (9) (8), (9), (6), (k), (d), 1 and (c), 144087-SP-20091119-2 -37- 201019951 〇j a combination of (8), (1) and (c) '(kk)(8), 1, (1) and (c), a combination of (11)1, (a), (1) and (c) to form a compound of the formula selected from the group consisting of: Wherein and T are as defined herein. 144087-SP-20091119-2 38- 201019951 IV. Designation of the representative representative: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 5. If there is a chemical formula in this case, please disclose The chemical formula that best shows the characteristics of the invention: P 144087-SP-20091119-1